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Nitric Oxide Synthesis and Regional Cerebral Blood Flow Responses to Hypercapnia and Hypoxia in the Rat

February 1993
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 13(1):80-7

February 1993
13(1):80-7

DOI:10.1038/jcbfm.1993.10

Source
PubMed

Authors:

Heidi M Koenig

University of Louisville

The role of nitric oxide (NO) synthesis in the cerebral hyperemic responses to hypercapnia and hypoxia was investigated in anesthetized rats. Regional CBF (rCBF) measurements were obtained in the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) using radiolabeled microspheres. The rCBF responses to either hypercapnia (PaCO2 = 70-80 mm Hg) or hypoxia (PaO2 = 40-45 mm Hg) were compared in rat groups studied in the presence and absence of NO synthase inhibition induced via the intravenous infusion of nitro-L-arginine methyl ester (L-NAME, 3 mg kg-1 min-1). Administration of L-NAME under normocapnic/normoxic conditions produced a 40-60% reduction in baseline rCBF values, indicating the presence of a NO "tone" in the cerebral vasculature. Infusion of L-NAME resulted in a substantial attenuation, in all regions measured, of the rCBF increases that normally accompany hypercapnia. In comparing saline-infused to L-NAME-infused rats, the percentage increases in rCBF (from normocapnic baseline values) were 351% versus 166% (CX), 446% versus 199% (SC), 443% versus 206% (BS), and 483% versus 174% (CE), respectively. The rCBF changes from baseline (delta rCBF in ml 100 g-1 min-1) were 488 versus 57 (CX), 570 versus 60 (SC), 434 versus 72 (BS), and 393 versus 45 (CE), respectively. These differences were all statistically significant (p < 0.05). During hypoxia, when compared to rats not given L-NAME, inhibition of NO synthase activity resulted in significantly greater (p < 0.05) percentage increases in rCBF (from normoxic baseline values) in most regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional cerebral blood flow (rCBF) values in the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) during hypercapnia, with (left) and without (right) intra venous infusion of the NO synthase inhibitor, L-NAME. All rCBF values during hypercapnia + L-NAME were signifi cantly lower than those measured during hypercapnia alone. Additional information is provided in the text. All values are means ± SD. *p < 0.05 versus control (normocapnic saline infusion); #p < 0.05 versus L-NAME (normocapnic).

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. Arterial blood variables

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Regional cerebrovascular resistance (CVR) values calculated for the groups represented in Fig. 1. Values are means ±SO. 'p < 0.05 versus control; #p < 0.05 versus the hypercapnic CVR value in the L-NAME-treated group.

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Regional CVR values calculated for the groups rep resented in Fig. 3. Values are means ::t SO. *p < 0.05 versus control.

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. .Regional CBF values measured, in normocapnic/ normoxlc rats, during saline infusion (rCBF values at 0 min) and at 10 and 20 min of intravenous L-NAME. Values are means::t SO.

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Figures - uploaded by Heidi M Koenig

Content may be subject to copyright.

Content uploaded by Heidi M Koenig

Content may be subject to copyright.

    

         

      

       

      

         

     

        

 

       

      

     

      

        

  



      

      

 

       

         

       

      

      

      

      

 

        

      

  

 

     

     

  

       

      

      

   

        

 

       

      

      

       

    

        

 



        

    

 

   



      

       

      

      

        

      



        

  

        

 

        

       

       

 

   



       

   

      

      

       

  

 

       

        

      



  



  

     

  



    

     

      



     

    



       

     

       

 

       

    



 



       

       

        

       



       

      

    

 

  

    



     

      

       

        







      

 

   

        

    

       

      

      

  

        

      

    



  

      

 

        

        

        



       



 

       

   

   

       

 

      

  

         

 

      



        

        

 

       

        

       

       

 

       



       





      

 

         

 

     

      

       



  

    

         



   

  

    

      

       



   

        

       

       

   

         

      

 



        

        

 

       

     

     

  

      

      



     

      



        

       

     

     

  

     

   

  

    



    

    



  

    





    

     

  

     

         

 





  

 





 

   

     

      

 

     

    

       



      

        

       

      

 

 



        

       

        

      

 

       

      

   

     

      



   

 



  

     

         

      

    

      

    

      

        



     

      

    

      

      

 

     

    

    

      



 

    

       

     

 

        

    

    

     

  

      

       

          

    

  

        

      

 



 

 



 





 

 

 



 



 

 

 

 

 



�   

  

  



  

 





 





 

         

      

     

        

       



         

        

     

     

       



   

        

                      



                       

                       



                        

         

                

  

        



   

     

    



       

      

       

 

     

      

    

 

   

      



 

      





      







 

 



 

 

 



 



 

 

 

 

 

 













       

    

      

         

          

      

        

     



    

     

 

     



 

       

    

 

       

        

       

      

       

 

       

       

  

  

 



 

 

 









 

 

   

   

  

   

 

        

    

          

       



     

     



 

       

  





    



  

       



      

       

      



        

    

         

        

  

  

       

       

    

     

      

    

      

         

 





      

      



      

       

 

 

 



 



 

 

 



 

 

 

 

  

   



 

 

 

   

 

         

         



      





 





 





























 

 

 

 

  

 

       

        

          

 

      

  

   

     

 

         

  

       

    

       

 

      

   

   

       

       



   

      



     



     

  



       





       

       

       

 

  

     

  

    

       



      

 

     

  

      

     

      

 

     

        



       

     

      

     

    

     

    

    









   

    

      

     



    

      

       

     

     

       



   



 

       

 

       

 



      

       

     

    

     

   

   

    

      

    



    

     

      

      

    

  

     

  



 

      

    

    

    



 

       

   

       

      

       

  

      

  

 

 

  

     

     



   

      

        





   

       

  

  

   

        

   

     



      



     

  

    

 

 

       

 

        

    

      



      

   

    

      

  

 

    

         



       

     

 

         



       

         

 

      

        

    

        

      

        

        

      

   

     

     

      

      

   

      

      

  

      





    

     

      

      

    

      

       

       

      

       

    



     

      

      

   

       

   

       

     

       



     

    

 

  

        

      

  

  

   

    

     



   

       

       

      



 

      

        

        



  

         



       

 

     

   

     

    

  



        

   

 

        

       

 

       

    

     



    

      

     

    

    



  

         

 

     

   

       

   

      

      

     

     

   

     

  

       

     

           

     

   

    

        

   

   





         



  

        

         

   

         

 

       

        



      

         



          

      



    

    

         



    

 



       

       

    

   

    

    

      

   

 

       

 

   



  

        



        

      

  

     

     



       

       

      

   

       

 

  

     

  

      

     

     

  

          

     

 

   

        

        

 

        

      

   

   

          

      



    

        

    



      

    





     

      



       

        

   

      



       





       

      

        

    

       

  

        



          

       

      



         

      

  

       

 

         

    

     

       

 

    

         

   

  

   



   

       

  

     

 

          

      

   



        

   

     

On the mechanisms of brain blood flow regulation during hypoxia

Article

Full-text available

Jun 2024
J PHYSIOL-LONDON

The brain requires an uninterrupted supply of oxygen and nutrients to support the high metabolic needs of billions of nerve cells processing information. In low oxygen conditions, increases in cerebral blood flow maintain brain oxygen delivery, but the cellular and molecular mechanisms responsible for dilation of cerebral blood vessels in response to hypoxia are not fully understood. This article presents a systematic review and analysis of data reported in studies of these mechanisms. Our primary outcome measure was the percent reduction of the cerebrovascular response to hypoxia in conditions of pharmacological or genetic blockade of specific signaling mechanisms studied in experimental animals or in humans. Selection criteria were met by 28 articles describing the results of animal studies and six articles describing the results of studies conducted in humans. Selected studies investigated the potential involvement of various neurotransmitters, neuromodulators, vasoactive molecules and ion channels. Of all the experimental conditions, blockade of adenosine‐mediated signaling and inhibition of ATP‐sensitive potassium (KATP) channels had the most significant effect in reducing the cerebrovascular response to hypoxia (by 49% and 37%, respectively). Various degree reductions of the hypoxic response were also reported in studies which investigated the roles of nitric oxide, arachidonic acid derivates, catecholamines and hydrogen sulphide, amongst others. However, definitive conclusions about the importance of these signaling pathways cannot be drawn from the results of this analysis. In conclusion, there is significant evidence that one of the key mechanisms of hypoxic cerebral vasodilation (accounting for ∼50% of the response) involves the actions of adenosine and modulation of vascular KATP channels. However, recruitment of other vasodilatory signaling mechanisms is required for the full expression of the cerebrovascular response to hypoxia. image

Nitric oxide and the brain. Part 1: Mechanisms of regulation, transport and effects on the developing brain

Article

Full-text available

Jun 2020

Apart from its known actions as a pulmonary vasodilator, nitric oxide (NO) is a key signal mediator in the neonatal brain. Despite the extensive use of NO for pulmonary artery hypertension (PAH), its actions in the setting of brain hypoxia and ischemia, which co-exists with PAH in 20–30% of affected infants, are not well established. This review focuses on the mechanisms of actions of NO covering the basic, translational, and clinical evidence of its neuroprotective and neurotoxic properties. In this first part, we present the physiology of transport and delivery of NO to the brain and the regulation of cerebrovascular and systemic circulation by NO, as well the role of NO in the development of the immature brain. NO can be transferred from the site of production to the site of action rapidly and affects the central nervous system. Inhaled NO (iNO), a commonly used medication, can have significant effects on the neonatal brain. NO regulates the cerebrovascular and systemic circulation and plays a role in the development of the immature brain. This review describes the properties of NO under physiologic conditions and under stress. The impact of this review is that it describes the effects of NO, especially regarding the vulnerable neonatal brain, and helps understand the conditions that could contribute to neurotoxicity or neuroprotection.

Globins and nitric oxide homeostasis in fish embryonic development

Article

Full-text available

Nov 2019
MAR GENOM

Since the discovery of new members of the globin superfamily such as Cytoglobin, Neuroglobin and Globin X, in addition to the most well-known members, Hemoglobin and Myoglobin, different hypotheses have been suggested about their function in vertebrates. Globins are ubiquitously found in living organisms and can carry out different functions based on their ability to bind ligands such as O2, and nitric oxide (NO) and to catalyze reactions scavenging NO or generating NO by reducing nitrite. NO is a highly diffusible molecule with a central role in signaling important for egg maturation, fertilization and early embryonic development. The globins ability to scavenge or generate NO makes these proteins ideal candidates in regulating NO homeostasis depending on the micro environment and tissue NO demands. Different amounts of various globins have been found in zebrafish eggs and developing embryos where it's unlikely that they function as respiratory proteins and instead could play a role in maintaining embryonic NO homeostasis. Here we summarize the current knowledge concerning the role of NO in adult fish in comparison to mammals and we discuss NO function during embryonic development with possible implications for globins in maintaining embryonic NO homeostasis.

Effect of Chronic Hypoxia on Carotid Vascular Responses to Adenosine in Rats

Article

Jun 2010

Nisreen Abo-Elmaaty

Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation

Article

Jan 2019
PHYSIOL REV

Nitric oxide (NO) is a small free radical with critical signaling roles in physiology and pathophysiology. The generation of sufficient NO levels to regulate the resistance of the blood vessels and hence the maintenance of adequate blood flow is critical to the healthy performance of the vasculature. A novel paradigm indicates that classical NO synthesis by dedicated NO synthases is supplemented by nitrite reduction pathways under hypoxia. At the same time, reactive oxygen species (ROS), which include superoxide and hydrogen peroxide, are produced in the vascular system for signaling purposes, as effectors of the immune response, or as byproducts of cellular metabolism. NO and ROS can be generated by distinct enzymes or by the same enzyme through alternate reduction and oxidation processes. The latter oxidoreductase systems include NO synthases, molybdopterin enzymes, and hemoglobins, which can form superoxide by reduction of molecular oxygen or NO by reduction of inorganic nitrite. Enzymatic uncoupling, changes in oxygen tension, and the concentration of coenzymes and reductants can modulate the NO/ROS production from these oxidoreductases and determine the redox balance in health and disease. The dysregulation of the mechanisms involved in the generation of NO and ROS is an important cause of cardiovascular disease and target for therapy. In this review we will present the biology of NO and ROS in the cardiovascular system, with special emphasis on their routes of formation and regulation, as well as the therapeutic challenges and opportunities for the management of NO and ROS in cardiovascular disease.

Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex

Article

Aug 1999

We investigated the role of nitric oxide (NO)/cGMP in the coupling of neuronal activation to regional cerebral blood flow (rCBF) in α-chloralose-anesthetized rats. Whisker deflection (60 s) increased rCBF by 18 ± 3%. NO synthase (NOS) inhibition by Nω-nitro-l-arginine (l-NNA; topically) reduced the rCBF response to 9 ± 4% and resting rCBF to 80 ± 8%. NO donors [ S-nitroso- N-acetylpenicillamine (SNAP; 50 μM), 3-morpholinosydnonimine (10 μM)] or 8-bromoguanosine 3',5'-cyclic-monophosphate (8-BrcGMP; 100 μM)] restored resting rCBF andl-NNA-induced attenuation of the whisker response in the presence ofl-NNA, whereas the NO-independent vasodilator papaverine (1 mM) had no effect on the whisker response. Basal cGMP levels were decreased to 35% byl-NNA and restored to 65% of control by subsequent SNAP superfusion. Inhibition of neuronal NOS by 7-nitroindazole (7-NI; 40 mg/kg ip) or soluble guanylyl cyclase by 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 100 μM) significantly reduced resting rCBF to 86 ± 8 and 92 ± 10% and whisker rCBF response to 7 ± 4 and 12 ± 3%, respectively. ODQ reduced tissue cGMP to 54%. 8-BrcGMP restored the whisker response in the presence of 7-NI or ODQ. We conclude that NO, produced by neuronal NOS, is a modulator in the coupling of neuronal activation and rCBF in rat somatosensory cortex and that this effect is mainly mediated by cGMP.l-NNA-induced vasomotion was significantly reduced during increased neuronal activity and after restoration of basal NO levels, but not after restoration of cGMP.

Recent insights into mechanisms of hypoxia-induced vasodilatation in the human brain

Article

Sep 2023
J PHYSIOL-LONDON

The cerebral vasculature manages oxygen delivery by adjusting arterial blood in-flow in the face of reductions in oxygen availability. Hypoxic cerebral vasodilatation, and the associated hypoxic cerebral blood flow reactivity, involve many vascular, erythrocytic and cerebral tissue mechanisms that mediate elevations in cerebral blood flow via micro- and macrovascular dilatation. This contemporary review focuses on in vivo human work - with reference to seminal preclinical work where necessary - on hypoxic cerebrovascular reactivity, particularly where recent advancements have been made. We provide updates with the following information: in humans, hypoxic cerebral vasodilatation is partially mediated via a - likely non-obligatory - combination of: (1) nitric oxide synthases, (2) deoxygenation-coupled S-nitrosothiols, (3) potassium channel-related vascular smooth muscle hyperpolarization, and (4) prostaglandin mechanisms with some contribution from an interrelationship with reactive oxygen species. And finally, we discuss the fact that, due to the engagement of deoxyhaemoglobin-related mechanisms, reductions in O2 content via haemoglobin per se seem to account for ∼50% of that seen with hypoxic cerebral vasodilatation during hypoxaemia. We further highlight the issue that methodological impediments challenge the complete elucidation of hypoxic cerebral reactivity mechanisms in vivo in healthy humans. Future research is needed to confirm recent advancements and to reconcile human and animal findings. Further investigations are also required to extend these findings to address questions of sex-, heredity-, age-, and disease-related differences. The final step is to then ultimately translate understanding of these mechanisms into actionable, targetable pathways for the prevention and treatment of cerebral vascular dysfunction and cerebral hypoxic brain injury.

Nitric oxide synthase inhibition in healthy adults reduces regional and total cerebral macrovascular blood flow and microvascular perfusion

Article

Full-text available

Oct 2021
J PHYSIOL-LONDON

The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region‐specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L‐NMMA, administered in a randomized, single‐blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L‐NMMA (or volume‐matched saline) was infused intravenously for 5 min prior to imaging. L‐NMMA reduced CBF (L‐NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5–7%) in anterior and posterior cerebral circulations, due in part to the reduced cross‐sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L‐NMMA (L‐NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7–11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. Key points Cerebral blood flow (CBF) is vital for brain health, but the signals that are key to regulating CBF remain unclear. Nitric oxide (NO) is produced in the brain, but its importance in regulating CBF remains controversial since prior studies have not studied all regions of the brain simultaneously. Using modern MRI approaches, a drug that inhibits the enzymes that make NO (L‐NMMA) reduced CBF by up to 11% in different brain regions. NO helps maintain proper CBF in healthy adults. These data will help us understand whether the reductions in CBF that occur during ageing or cardiovascular disease are related to shifts in NO signalling.

Purification of pig brain methionine synthase and its control and regulation by nitric oxide

Thesis

Jan 2001

John M. Gibbons

The vitamin B12 network links the folate and sulphur amino acid pathways with, the synthesis of polyamines and lipid biosynthesis. The role that this vitamin plays within human disease has been linked to a variety of haematological, developmental, neurological and pathological conditions such as cancer and heart disease. The role of nitric oxide within the body has also been shown to be extensive. The physiological effects range from cardiovascular function, peripheral nervous system, central nervous system, and the immune system. The pathophysiological actions include, septic shock, reperfusion injury, arteriosclerosis, hypertension, and neurotoxicity. In order to better study and identify neurological disorders linked to B12, the mammalian B12 dependent methionine synthase enzyme was purified. The enzyme appears under native conditions to be 155kd in weight composed of several subunits (94 and 36 Kd). The pi for the enzyme was determined to be 4.3 and 5.1. Concurrent with the purification work, studies were done to determine some of the biological effects of NO. NO inhibits B12 MS with an IC50 of 3 μM. A comparison between the effects of NO and N2O on B12 MS inhibition both of which inhibit B12 MS in a dose dependent manner and irreversibly. To contrast these studies a comparison of the effects of NO and N2O on cGMP synthesis. NO stimulates the production of cGMP while NO was found to have no significant effect. The production of NO was also studied in vivo and in vitro to determine the effect of changes in oxygen partial pressures. NO synthesis in vivo was measured using the production of nitrate and nitrite in plasma and measured by capillary electrophoresis. When human volunteers were exposed to 2.8 bar levels of nitrate increased 4.2 times above background.

Regulation of the Cerebral Circulation by Arterial Carbon Dioxide

Chapter

Jun 2019

Intact, coordinated, and precisely regulated cerebrovascular responses are required for the maintenance of cerebral metabolic homeostasis, adequate perfusion, oxygen delivery, and acid‐base balance during deviations from homeostasis. Increases and decreases in the partial pressure of arterial carbon dioxide (PaCO2) lead to robust and rapid increases and decreases in cerebral blood flow (CBF). In awake and healthy humans, PaCO2 is the most potent regulator of CBF, and even small fluctuations can result in large changes in CBF. Alterations in the responsiveness of the cerebral vasculature can be detected with carefully controlled stimulus‐response paradigms and hold relevance for cerebrovascular risk in steno‐occlusive disease. As changes in PaCO2 do not typically occur in isolation, the integrative influence of physiological factors such as intracranial pressure, arterial oxygen content, cerebral perfusion pressure, and sympathetic nervous activity must be considered. Further, age and sex, as well as vascular pathologies are also important to consider. Following a brief summary of key historical events in the development of our understanding of cerebrovascular physiology and an overview of the measurement techniques to index CBF this review provides an in‐depth description of CBF regulation in response to alterations in PaCO2. Cerebrovascular reactivity and regional flow distribution are described, with further consideration of how differences in reactivity of parallel networks can lead to the “steal” phenomenon. Factors that influence cerebrovascular reactivity are discussed and the mechanisms and regulatory pathways mediating the exquisite sensitivity of the cerebral vasculature to changes in PaCO2 are outlined. Finally, topical avenues for future research are proposed. © 2019 American Physiological Society. Compr Physiol 9:1101‐1154, 2019.

ORIGIN AND DISTRIBUTION OF NITRIC-OXIDE SYNTHASE-IMMUNOREACTIVE NERVE-FIBERS IN RAT CEREBRAL-ARTERIES

Article

Full-text available

Jan 1992

Suppression by NG-Monomethyl-L-Arginine of Cerebroarterial Responses to Nonadrenergic, Noncholinergic Vasodilator Nerve Stimulation

Article

Jan 1991

Relaxations caused by electrical and chemical (nicotine) stimulation of nonadrenergic, noncholinergic nerves are not influenced in dog cerebral arteries made tachyphylactic to peptides, such as vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and atrial natriuretic peptide (ANP), but are abolished by oxyhemoglobin and methylene blue. Treatment with N G -monomethyl-L-arginine (L-NMMA), a itric oxide (NO) synthesis inhibitor, suppresses the relaxant response to vasodilator nerve stimulation, whereas D-NMMA is ineffective.

The potent vasodilating and guanylyl cyclase activating dintrosyl-iron(II) complex is stored in a protein-bound form in vascular tissue and is released by thiols

Article

Jan 1993

Brain adenosine hypoxia in rats concentration during

Article

Jan 1981
AM J PHYSIOL-HEART C

Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase.

Article

Jan 1989

Nitric Oxide: Physiology, Pathophysiology, and Pharmacology

Article

Jun 1991

Localization of nitric oxide syn-thase indicating a neural role for nitric oxide

Article

Jan 1990
NATURE

The effect of ketamine hydrochloride (kh) on cerebral blood flow (cbf) during acute hypoxia

Article

Sep 1991
J NEUROSURG ANESTH

Microvascular Effects of Local or Systemic Inhibition of Endogenous Endothelium-Derived Relaxing Factor (Nitric Oxide) Production

Article

Jan 1991

The objective was to investigate microvascular effects of inhibition of endogenous nitric oxide (NO) production in rabbit skeletal muscle in vivo. Intravital microscopy of the tenuissimus muscle and recording of arterial blood pressure were performed in anesthetized rabbits. Topical administration of N(G)-monomethyl-L-arginine (L-NMMA, 10-100-mu-M) or i.v. infusion of N-omega-nitro-L-arginine methyl ester (L-NAME, 1-100 mg/kg) elicited dose-dependent vasoconstriction of the skeletal muscle microvessels. During i.v. L-NAME, a dose-dependent increase in systemic blood pressure was observed. The effects of topical L-NMMA or systemic L-NAME were reversed by i.v. infusion Of L-arginine (1 g/kg) but not D-arginine. Vasodilation by topical acetylcholine, but not nitroprusside or adenosine, was inhibited by L-NMMA or L-NAME. The vasodilation in response to muscle contractions induced by motor nerve stimulation as well as the vasodilator response elicited by graded perfusion pressure reductions were unaffected by L-NAME or L-NMMA administered topically. Our results indicate that endogenous NO formed from L-arginine is a modulator of resting microvascular tone in vivo, whereas under the present conditions we were unable to demonstrate a role for endogenous NO in myogenic vasodilatation or functional hyperemia.

Does Nitric Oxide Mediate the Increases in Cerebral Blood Flow Elicited by Hypercapnea?

Article

Apr 1993
Surv Anesthesiol

Costantino Iadecola

Nitric Oxide Synthesis and Regional Cerebral Blood Flow Responses to Hypercapnia and Hypoxia in the Rat

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