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Treatment of hypertension with ascorbic acid
Abstract
In a randomised, double-blind, placebo-controlled study we showed that treatment of hypertensive patients with ascorbic acid lowers blood pressure. Further studies of ascorbic acid to treat hypertension, with clinical endpoints, are warranted.
... The activation of AT1r increases the production of reactive oxygen species (ROS), which are implicated in the development and/or maintenance of hypertension in humans and animal models, including the renovascular 2K1C hypertension and SHRs [9][10][11][12]. ROS are molecules derived from oxygen that, in low concentration, can act as cellular signaling to regulate biological function [13][14][15]. ...
... The administration of molecules capable of inhibiting the production and effects of ROS, such as apocynin, is likely to improve pathological conditions [12,[34][35][36]. Chronic treatment of SHRs with apocynin reduced MAP and prevented endothelial dysfunction by increasing intracellular calcium and nitric oxide concentrations in endothelial cells [37]. ...
Background:
A growing body of evidence suggests that oxidative stress plays a role in the pathophysiology of hypertension. However, the involvement of the reactive oxygen species (ROS) in the commissural nucleus of the solitary tract (commNTS) in development the of hypertension remains unclear.
Method:
We evaluated the hemodynamic and sympathetic responses to acute inhibition of NADPH oxidase in the commNTS in renovascular hypertensive rats. Under anesthesia, male Holtzman rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip (2K1C) hypertension. After six weeks, these rats were anesthetized and instrumented for recording mean arterial pressure (MAP), renal blood flow (RBF), renal vascular resistance (RVR), and renal sympathetic nerve activity (RSNA) during baseline and after injection of apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor), NSC 23766 (RAC inhibitor) or saline into the commNTS.
Results:
Apocynin into the commNTS decreased MAP, RSNA, and RVR in 2K1C rats. NSC 23766 into the commNTS decreased MAP and RSNA, without changing RVR in 2K1C rats.
Conclusion:
These results demonstrate that the formation of ROS in the commNTS is important to maintain sympathoexcitation and hypertension in 2K1C rats and suggest that NADPH oxidase in the commNTS could be a potential target for therapeutics in renovascular hypertension.
... Humans, essential hypertension [38, [156][157][158]. Systolic blood pressure (SBP) ⬇, endothelial vasodilation ⬆, arterial stiffness ⬇ [38, [156][157][158]. ...
... Humans, essential hypertension [38, [156][157][158]. Systolic blood pressure (SBP) ⬇, endothelial vasodilation ⬆, arterial stiffness ⬇ [38, [156][157][158]. Humans, mild hypertension [159]. ...
As a major cause of morbidity and mortality globally, hypertension remains a serious threat to global public health. Despite the availability of many antihypertensive medications, several hypertensive individuals are resistant to standard treatments, and are unable to control their blood pressure. Regulation of the renin-angiotensin-aldosterone system (RAAS) controlling blood pressure, activation of the immune system triggering inflammation and production of reactive oxygen species, leading to oxidative stress and redox-sensitive signaling, have been implicated in the pathogenesis of hypertension. Thus, besides standard antihypertensive medications, which lower arterial pressure, antioxidant medications were tested to improve antihypertensive treatment. We review and discuss the role of oxidative stress in the pathophysiology of hypertension and the potential use of antioxidants in the management of hypertension and its associated organ damage.
... Vitamin E [16,17] may modulate the interactions between cytochrome b558, the membranebound part of nicotinamide adenine dinucleotide (P) H oxidase that is essential for both the activity and stability of the enzyme. The previous studies have proved that in mild-to-moderate hypertensive patients, supplementation with ascorbic acid (500 mg/day) significantly improved systolic and diastolic BP (DBP) [18] and increased plasma high-density lipoprotein (HDL) cholesterol in female. The aim of the study is to explore the effect of Vitamin C and Vitamin E on hypertension and to conclude which vitamin supplement will be a better choice for hypertension. ...
... The major findings of our study are that Vitamin C and E had a mild positive effect on BP. In recent studies, it is proved that Vitamin C improves nitric oxide bioactivity [18,19] which is a potent vasodilator and can reduce the BP. This is seen to a lesser extent in our study due to the time factor and fewer subjects. ...
Objective: Both Vitamin C and Vitamin E supplementation were associated with reduction in blood pressure (BP) in observational studies, although, results of clinical trials are inconsistent. The objective of our study is to conduct a clinical trial to observe the effects of oral supplementation of Vitamin C and Vitamin E on BP. Methods: About 60 non-teaching staffs of our college with systolic BP more than 130 mmHg and diastolic BP more than 90 mmHg were taken as subjects and divided into two groups. Initial BP and BP after oral Vitamin C, 500 mg/day for a period of 12weeks to Group 1 and initial BP and BP after oral Vitamin E, 200 IU/day, for a period of 12 weeks to Group 2 were recorded. Results: Statistical analysis was done by paired t-test, analysis of variance (ANOVA), and least significant difference (LSD) tests. *p<0.05 was considered statistically significant. Systolic 2 and diastolic 2 – after 3 months of supplementation showed 0.161 and 0.161 which is not significant. ANOVA and LSD tests show no significant results. Conclusion: Long-term trials on the effects of Vitamin C and Vitamin E supplementation on BP and clinical events are needed.
... (3) Multivitamin supplementation was associated with improvement of surrogate vascular outcomes of endothelial dysfunction. For example, after vitamin C or a combination of vitamin C and E supplementation, levels of FMD, augmentation index, central aortic pressure, (4) lipid peroxidation, (5,6) and blood pressure (7) were improved. Supplementation of folic acid, alone or combined with other B vitamins, was also associated with improved endothelial function via lowering plasma homocysteine levels, (8,9) or even independent of homocysteine-lowering. ...
... Supplementation of folic acid, alone or combined with other B vitamins, was also associated with improved endothelial function via lowering plasma homocysteine levels, (8,9) or even independent of homocysteine-lowering. (10) However, most previous studies were conducted on patients with coronary artery disease (CAD), (4,(7)(8)(9)(10) and with a very high supplementation dosage that cannot be obtained normally via diet alone. (4,5,10) Evidence regarding the effects of low-dose supplementation in non-CAD patients on the biomarkers related to endothelial function is limited. ...
There is limited evidence examining the association between B vitamin supplementation and improved endothelial function via lowering plasma homocysteine levels. This study investigated whether low-dose B vitamin supplementation improves endothelial dysfunction in Japanese adults with one or more components of metabolic syndrome. A randomized, controlled, crossover trial, without a washout period or blinding of subjects, was conducted from May-September, 2010. The subjects were 127 Japanese men and women aged 40–65 years who had at least one component of metabolic syndrome without medication. Participants took a supplement drink for two months but were divided into Early Intervention or Later Intervention groups. The flow-mediated dilatation, plasma homocysteine level, serum B-vitamins, and vitamin C levels were measured. A significant increase in serum B vitamins and vitamin C levels, and a reduction in plasma homocysteine levels were observed. The mean serum homocysteine level pre- and post-intervention was 9.8 and 8.2 µmol/L in the Early Intervention group and 10.8 and 7.4 µmol/L in the Later Intervention group (p<0.01). However, no significant changes in flow-mediated dilatation was found. Low-dose multivitamin supplementation including B vitamins is associated with a significant reduction in plasma homocysteine levels among patients with one or more components of metabolic syndrome. This study was registered at the University Hospital Medical Information Network (UMIN) centre, and has the identifier UMIN000004436.
... In a rat model designed to simulate myocardial infarction, the administration of omega-3 supplementation yielded a notable decrease in the size of the infarcted region. Flavanols, such as quercetin, have exhibited the capacity to reduce indicators of oxidative stress and enhance heart function in both animal models and patients diagnosed with cardiovascular disease [133]. There exists a notable correlation between heightened intake of flavonoids and decreased mortality rates linked to coronary heart disease in the senior demographic. ...
Flavonoids, which are a heterogeneous class of polyphenolic chemicals found in various plant species, have attracted considerable scientific interest due to their potential therapeutic effects, particularly in the context of cardiovascular health. Numerous scientific investigations have provided evidence that flavonoids exhibit the ability to effectively scavenge reactive oxygen species (ROS), modulate the functions of antioxidant enzymes, and inhibit the generation of ROS. Consequently, these mechanisms help in the reduction of oxidative stress's impact on cardiovascular well-being. The therapeutic benefits of flavonoids are facilitated through their capacity to engage in direct interactions with ROS, thereby diminishing their reactivity and constraining their deleterious impact on cellular constituents. Furthermore, it has been shown that flavonoids have the capacity to induce the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor renowned for its role in regulating the expression of diverse antioxidants and genes implicated in cellular
... In a rat model designed to simulate myocardial infarction, the administration of omega-3 supplementation yielded a notable decrease in the size of the infarcted region. Flavanols, such as quercetin, have exhibited the capacity to reduce indicators of oxidative stress and enhance heart function in both animal models and patients diagnosed with cardiovascular disease [133]. There exists a notable correlation between heightened intake of flavonoids and decreased mortality rates linked to coronary heart disease in the senior demographic. ...
Flavonoids, which are a heterogeneous class of polyphenolic chemicals found in various plant species, have attracted considerable scientific interest due to their potential therapeutic effects, particularly in the context of cardiovascular health. Numerous scientific investigations have provided evidence that flavonoids exhibit the ability to effectively scavenge reactive oxygen species (ROS), modulate the functions of antioxidant enzymes, and inhibit the generation of ROS. Consequently, these mechanisms help in the reduction of oxidative stress's impact on cardiovascular well-being. The therapeutic benefits of flavonoids are facilitated through their capacity to engage in direct interactions with ROS, thereby diminishing their reactivity and constraining their deleterious impact on cellular constituents. Furthermore, it has been shown that flavonoids have the capacity to induce the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor renowned for its role in regulating the expression of diverse antioxidants and genes implicated in cellular
... In our study it was observed there is a significant reduction in post prandial blood sugar & HbA1c (%) in test group supplemented with Vitamin C & E for 3 months. In recent studies, it is proved that Vitamin C improves nitric oxide bioactivity 10,11 which is a potent vasodilator and can reduce the BP. This is seen to a lesser extent in our study due to the time factor and fewer subjects. ...
Background: Antioxidants scavenge free radicals to reduce oxidative stress in diabetes and hypertension. Our aim of our study was use of vit-C and vit-E on blood glucose, glycosylated haemoglobulin, serum lipid levels in diabetic and hypertensive patients. Materials & Methods: This is a prospective interventional study in known Diabetic and Hypertensive subjects. The equal subjects (N=140 each) were divided into two groups, diabetic group (group I) and hypertensive group (group II). Each Group were divided into Control Group who received standard treatment of Diabetes with Oral Hypoglycaemic drugs & anti-hypertensive drugs (n=70) & Test Group which received supplementation with antioxidants tablet Limcee (Vitamin C) of 500 mg & Tablet Evion (Vitamin E) of 400 mg orally in addition to standard treatment for 12 weeks. Blood samples were collected before and after supplementation for 12 weeks, blood sugar, HbA1c, lipid profile and blood pressure were measured. Data collected analyzed by SPSS 22. P values of <0.05 was considered significant. Results: Total Number of subjects was 280, out of which 140 participants 65.7 % were males in test group and 34.2% were females. Maximum number (77.5%) of hypertensives in Test Group 1 & 34.2% were females.
... One possible reason is that the free contractile response to norepinephrine is increased in patients with hypertension, which can be reduced by vitamin C (148). However, in several large-scale clinical trials, the effect of supplementation of vitamin C on blood pressure was unpredictable and more experiments are needed to confirm the exact effect (161)(162)(163), which may result from the reduced bioavailability of NO. B-cell lymphoma 6 (BCL6) is known as a key intervention target for autoimmune diseases by inhibiting production of ROS and apoptosis (149); however, it is unclear whether this can reduce hypertension. ...
Hypertension is regarded as the most prominent risk factor for cardiovascular diseases, which have become a primary cause of death, and recent research has demonstrated that chronic inflammation is involved in the pathogenesis of hypertension. Both innate and adaptive immunity are now known to promote the elevation of blood pressure by triggering vascular inflammation and microvascular remodeling. For example, as an important part of innate immune system, classically activated macrophages (M1), neutrophils, and dendritic cells contribute to hypertension by secreting inflammatory cy3tokines. In particular, interferon-gamma (IFN-γ) and interleukin-17 (IL-17) produced by activated T lymphocytes contribute to hypertension by inducing oxidative stress injury and endothelial dysfunction. However, the regulatory T cells and alternatively activated macrophages (M2) may have a protective role in hypertension. Although inflammation is related to hypertension, the exact mechanisms are complex and unclear. The present review aims to reveal the roles of inflammation, immunity, and oxidative stress in the initiation and evolution of hypertension. We envisage that the review will strengthen public understanding of the pathophysiological mechanisms of hypertension and may provide new insights and potential therapeutic strategies for hypertension.
... The ED contained vitamin C and taurine which serve as antioxidant/inflammatory agents [9,40,41]. Indeed, several studies revealed that the consumption of both vitamin C and taurine can significantly decrease BP [42][43][44]. Vitamin C functions in vascular endothelium and smooth muscle and increases vascular dilation and eventually BP reduction [45]. On the other hand, the consumption of taurine can increase endothelium-dependent and independent vasodilation [44,46]. ...
This study examined the effects of a non-caffeinated energy drink (ED) that contained calamansi juice, glucose, and taurine on 3-km running performance and recovery. Eleven NCAA Division I middle-distance runners (20.8 ± 1.5 years old) were randomly assigned to consume either the ED or a placebo drink 60 min before 3-km running on a 400-m official track. Performance time and speed were recorded every 500-m interval. Recovery blood lactate concentration (BLC), systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured at baseline, 60-min after ingesting the drinks, and post-running measurements were performed at 1-min, 5-min, and 10-min. Repeated analysis of variance and paired t-test were applied to examine the effects of time, trials, and their interaction on performance and recovery. Statistical significance was set a priori at p < 0.05. No significant difference was observed in performance time and speed between trials (p < 0.05). No interaction effect was found on performance time, speed, recovery BLC, DBP, and HR (p < 0.05). However, an interaction effect for trial by time was observed on SBP (p = 0.01). Recovery SBP continues to decrease from 5-min to 10-min in the ED trial (∆ = −13.9·mmHg) and slightly increased in the placebo trial (∆ = 1.1·mmHg). This study suggests that acute consumption of a calamansi-containing ED can positively impact the SBP recovery but not running performance. Further studies are needed to examine the acute and chronic effects of this ED on exercise performance and recovery among different populations.
... Patients consuming 2 g of ascorbic acid followed by 500 mg per day for 30 days had a signi icant 13-mm Hg decrease in systolic blood pressure, with no change in diastolic blood pressure. [8] A signi icant decrease in systolic (4.48 %) and diastolic blood pressure (3.60 %) was found in the participants supplemented with 250 mg Vitamin C and nutrition counselling. A hypolipidemic effect was also evident in Vitamin C supplemented group with 4.62% reduction in total cholesterol, 4.49 % in LDL-C, 6.11% in triglycerides and 6.11% in VLDL-C was also observed in the supplemented group as compared to that of control group along with an increase of 1.69 % in HDL-C. ...
... Vitamin C may have favorable effects on vascular dilation, possibly through its antioxidant effects on NO ( Duffy et al., 2001;Jackson et al., 1998;Vita et al., 1998). Nevertheless, there are several small and short-term clinical tri- als in which the effect of vitamin C supplements on blood pres- sure have yielded inconsistent findings ( Block et al., 2001;Duffy et al., 1999;Fotherby et al., 2000; Galley et al., 1997;Ghosh et al., 1994;Mullan et al., 2002). The lack of antihypertensive efficacy observed in studies using supplementation with vitamin C alone could be due to the decreased bioavailability of NO under condi- tions of oxidative stress. ...
Hypertension is a highly prevalent disease worldwide. It is known for being one of the most important risk factors for developing cardiovascular disease, including acute myocardial infarction and stroke. Therefore, during the last decades there have been multiple efforts to fully understand the mechanisms underlying hypertension, and then develop effective therapeutic interventions to attenuate the morbidity and mortality associated with this condition. In this regard, oxidative stress has been proposed as a key mechanistic mediator of hypertension, which is an imbalance between oxidant species and the antioxidant defense systems. A large amount of evidence supports the role of vascular wall as a major source of reactive oxygen species. These include the activation of enzymes, such as NADPH oxidase and xanthine oxidase, the uncoupling eNOS and mitochondrial dysfunction, having as a major product the superoxide anion. Among the stimuli that increase the production of oxidative species can be found the action of some vasoactive peptides, such as angiotensin II, endothelin-1 and urotensin II. The oxidative stress state generated leads to a decrease in the biodisponibility of nitric oxide and prostacyclin, key factors in maintaining the vascular tone. The knowledge of the mechanisms mentioned above has allowed generating some therapeutic strategies using antioxidants as antihypertensives with different results. Further studies are required to position antioxidants as key agents in the treatment of hypertension. The current review summarize evidence of the role of oxidative stress in hypertension, emphasizing in therapeutic targets that can be consider in antioxidant therapy.
© Georg Thieme Verlag KG Stuttgart · New York.
... In addition, vitamin C enhances erythrocyte Na + /K + ATPases, diuretic activities (Na + excretion), as well as involved in cytosolic Ca 2+ reduction (Ca channel blocker) and thus suppress the vascular constriction through regulating SNS and thus positively regulate BP [37,99]. Furthermore, vitamin C is reported to display potent antioxidant and anti-inflammatory activities, which might improve endothelial function by improving NO levels [100]. ...
Hypertension (HT) is one of the pivotal risk factors for various detrimental diseases like cardiovascular diseases (CVDs), cerebrovascular disease, and renal dysfunction. Currently, many researchers are paying immense attention to various diet formula (dietary approach) with a special focus on micro and macronutrients along with modified lifestyle and standard anti-hypertensive drugs. Micronutrients (minerals/vitamins) play a central role in the regulation of blood pressure (BP) as they aid the function of macronutrients and also improve the anti-hypertensive functions of some anti-hypertensive agents. Even though several studies have demonstrated the beneficial effects of micronutrients on controlling BP, still some ambiguity exists among the nutritionists/doctors, which combination or individual mineral (dietary approach) contributes to better BP regulation. Therefore, this critical review article was attempted to delineate the underlying role of micronutrients (minerals and vitamins) for the management and prevention or delaying of HT and their related complications with strong affirmation from clinical trials as well as its mechanism of controlling BP. Moreover, the major source and recommended daily allowance (RDA) of various micronutrients are included in this review for guiding common readers (especially HT subjects) and dieticians to choose/recommend a better micronutrient and their combinations (other nutrients and standard anti-hypertensive drugs) for lowering the risk of HT and its related co-morbid conditions like CVDs.
... The synthesis of free radicals have been identified to influence BP [11]; whilst exogenous administration of antioxidants has been used in animal models and in humans with hypertension to counteract the hypertensive effect of reactive oxygen species (ROS), due to their potential role in improving vascular function and reducing BP [12]. While several studies have suggested an inverse association between dietary antioxidants and BP [13][14][15][16][17][18][19][20][21][22], published results from randomized controlled clinical trials do not support the hypothesis that vitamin E or β-carotene supplementation has a protective effect on BP [23,24]. Relatedly, diets consist of a variety of foods, with complex combinations of antioxidant nutrients. ...
The association between dietary antioxidant quality score (DAQS) and cardiovascular risk factors such as low cardiovascular fitness (CRF) and elevated blood pressure (BP) has rarely been investigated. To investigate the association between DAQS, CRF, and BP. This cross-sectional study was conducted on 270 adult subjects living in Tehran, Iran. Dietary intake was evaluated using a validated food frequency questionnaire. The DAQS was calculated using antioxidant-nutrient intake. Socio-economic status, anthropometric measures, and BP were recorded by a trained interviewer, using standard methods. A significant increase was found in maximal oxygen uptake (p value = 0.01) across tertiles of DAQS. After adjusting for confounders, the association remained unchanged (p value = 0.02). Participants in the highest tertile of DAQS had higher systolic BP (SBP) (p value = 0.01) and diastolic BP (DBP) (p value = 0.03), although adjustment for confounding factors attenuated the results (p value = 0.3 for DBP and p value = 0.6 for SBP). Our results revealed that higher DAQS is associated with better CRF in Iranian adults. Further studies are needed to establish the veracity of our results.
... El segundo estudio incorporó a 39 individuos hipertensos que fueron divididos en un grupo que recibió una dosis inicial de VC de 2 gr y luego durante 30 días 500 mg/día. El grupo tratamiento redujo en forma significativa los valores de presión arterial sistólica comparado con el grupo placebo (309). ...
... Moderate intake fruits and vegetables that are rich in ascorbic acid (vitamin C) can lower the blood pressure, instead [450], and hence, ascorbic acid is a useful adjunctive therapy for effectively relieving hypertension [451][452][453][454]. Mullan et al [452] studied the hemodynamic effect of oral supplementation of ascorbic acid in a random double-blind trial and suggested that ascorbic acid lowers the blood pressure by enhancing endothelial nitric-oxide biological activity. ...
Phonon spectrometrics examination of the effect of pressure, temperature, molecular undercoordination, and charge injection by acid, base, and salt solvation establishes the regulations for the hydrogen bonding and electronic dynamics and the properties of the deionized water and aqueous solutions. Consistency between theory and measurements confirms the essentiality of the quasisolid phase of negative thermal expansion due to O:H–O segmental specific heat disparity, and the supersolid phase due to electrostatic polarization by ions injection or molecular undercoordination. Lewis acid and base solvation creates the H↔H anti–HB due to the excessive protons and the O:⇔:O super–HB because of the excessive lone pairs, respectively. The multifield mediation of the HB network results in anomalies of water ice and aqueous solutions such as ice friction, ice floating, regelation, superheating and supercooling, warm water speedy cooling, and critical conditions for phase transition. Extending the knowledge towards the deep engineering of liquid water would be promising.
... Vitamin C. Researchers have investigated the potential effects of vitamin C supplementation in the management of hypertension. The blood pressure-lowering effect of vitamin C was previously observed following treatment with 500 mg daily for 4 to 6 weeks in patients with hypertension (21,22). A meta-analysis including 29 clinical trials reported that vitamin C supplementation for 8 weeks on average reduced SBP and DBP by 3.8 mmHg and 1.5 mmHg, respectively (23). ...
... Moderate intake fruits and vegetables that are rich in ascorbic acid (vitamin C) can lower the blood pressure, instead [450], and hence, ascorbic acid is a useful adjunctive therapy for effectively relieving hypertension [451][452][453][454]. Mullan et al [452] studied the hemodynamic effect of oral supplementation of ascorbic acid in a random double-blind trial and suggested that ascorbic acid lowers the blood pressure by enhancing endothelial nitric-oxide biological activity. ...
Aqueous charge injection in forms of electrons, protons, lone pairs, ions, and molecular dipoles by solvation is ubiquitously important to our health and life. Pursuing fine-resolution detection and consistent insight into solvation dynamics and solute capabilities has become an increasingly active subject. This treatise shows that charge injection by solvation mediates the O:H–O bonding network and properties of a solution through O:H formation, H↔H fragilization,O:⇐⇒:Ocompression,electrostaticpolarization,H2Odipolar shielding, solute–solute interaction, and undercoordinated H–O bond contraction. A combination of the hydrogen bond (O:H–O or HB with ‘:’ being the electron lone pairs of oxygen) cooperativity notion and the differential phonon spectrometrics(DPS) has enabled quantitative information on the following: ....
... Moderate intake fruits and vegetables that are rich in ascorbic acid (vitamin C) can lower the blood pressure, instead [450], and hence, ascorbic acid is a useful adjunctive therapy for effectively relieving hypertension [451][452][453][454]. Mullan et al [452] studied the hemodynamic effect of oral supplementation of ascorbic acid in a random double-blind trial and suggested that ascorbic acid lowers the blood pressure by enhancing endothelial nitric-oxide biological activity. ...
An incorporation of the hydrogen bond cooperativity theory to the DPS strategy and surface stress (contact angle) detection could resolve the solvation bonding and nonbonding dynamics and solute capabilities. The enabled information includes bond length and stiffness transition, electron polarization, and the fraction of bonds transformed from the mode of ordinary water to the hydration shells. A combination of the DPS and the ultrafast IR spectroscopy would be more revealing towards solute-solvent and solute-solute molecular interactions, solute capabilities, and solution properties. The DPS is focused on the solvation O:H–O segmental cooperative bonding dynamics and the ultrafast IR on molecular motion dynamics by measuring phonon relaxation time.
... This support the hypothesis that both extracts are capable to directly target the smooth muscle cell and activate vasorelaxant mechanisms thus ensuring a persistent decrease of active muscle tone. Taking into account the chemical composition of the extracts, MSS vasoactivity is likely due to the presence of the vasodilating agents catechin and ascorbic acid (Duffy et al., 1999;Ghayur, Khan, & Hassan Gilani, 2007). On the other hand, GABA, which inhibits noradrenaline release from sympathetic nerves thus exerting an antihypertensive effect (Hayakawa, Kimura, & Kamata, 2002) and proline, by improving nitric oxide (NO) bioavailability, (Leal et al., 2019) may account for PSS vasodilation. ...
... Antioxidant treatment with ascorbic acid was initially shown to lower blood pressure in a limited number of patients with hypertension [391,392]. However, larger studies have not found a clear beneficial effect of antioxidant vitamins on the development or control of blood pressure [393,394]. ...
Hypertension is the most prevalent cause of cardiovascular disease and kidney failure, but only about 50% of patients achieve adequate blood pressure control, in part, due to inter-individual genetic variations in the response to antihypertensive medication. Significant strides have been made toward the understanding of the role of reactive oxygen species (ROS) in the regulation of the cardiovascular system. However, the role of ROS in human hypertension is still unclear. Polymorphisms of some genes involved in the regulation of ROS production are associated with hypertension, suggesting their potential influence on blood pressure control and response to antihypertensive medication. This review provides an update on the genes associated with the regulation of ROS production in hypertension and discusses the controversies on the use of antioxidants in the treatment of hypertension, including the antioxidant effects of antihypertensive drugs.
... Moderate intake fruits and vegetables that are rich in ascorbic acid (vitamin C) can lower the blood pressure, instead [450], and hence, ascorbic acid is a useful adjunctive therapy for effectively relieving hypertension [451][452][453][454]. Mullan et al [452] studied the hemodynamic effect of oral supplementation of ascorbic acid in a random double-blind trial and suggested that ascorbic acid lowers the blood pressure by enhancing endothelial nitric-oxide biological activity. ...
Charge injection in terms of anions, cations, electrons, lone pairs, protons, and molecular dipoles by acid,base, salt and organic molecular solvation mediates the O:HO bonding network and properties of the solution through O:H formation, HH fragillization, O:=:O compression, electrostatic polarization, H2O dipolar shielding, and solute/solute interaction
... [21] Ascorbic acid is a powerful antioxidant and essential against scurvy. Good results have also been achieved in hypertension treatment by Duffy et al. [22] , after supplementing hypertensive patients with ascorbic acid. Oral administration of citric acid may also ameliorate ketosis and protect against the development of diabetic complications. ...
The objective of the present work was to evaluate the effect of hot air convective drying on the organic acid profile of chestnut. An extractive method, with internal standard, followed by HPLC-UV was validated, allowing the quantification of malic, ascorbic, citric, and fumaric acids with good precision and accuracy. Fresh chestnuts presented differences between varieties. The thermal process caused equivalent losses of ascorbic acid on both varieties, but higher losses of malic acid in Longal. Furthermore, fumaric acid contents increased on both varieties. Therefore, hot air convective drying affected the organic acid composition of chestnut slices, and this effect was varietal dependent.
... These effects have been reported to be mediated by the antioxidant actions of vitamin C [6], which may play a role in iron absorption, gastric cancer prevention, vascular disease and hypertension [7]. Vitamin C can also protect and stimulate biosynthesis of endothelial nitric oxide (NO), which is important for vascular relaxation [8,9]. ...
Background:
The effect of the concomitant use of sodium benzoate (NaB) and ascorbic acid on human health remains controversial. Therefore, the current study is designed to investigate the effect of NaB and ascorbic acid on the testicular function of adult Wistar rats.
Methods:
Adult Wistar rats were randomly allotted into Control (vehicle; received 1 ml of distilled water), NaB-treated (SB-treated; received 100 mg/kg body weight;b.w), ascorbic acid-treated (AA-treated; received 150 mg/kgb.w) and NaB+ ascorbic acid-treated (SB+AA-treated) groups. The treatment lasted for 28 days and the administration was given orally. The body weight change was monitored. Semen analysis, biochemical assay and histological examination were performed.
Results:
Treatment with NaB significantly altered the cytoarchitecture of testicular tissue, sperm quality, testicular endocrine function and oxidative stress status without any alteration in body weight gain compared to control. In addition, treatment with NaB+ ascorbic acid exacerbated testicular tissue disruption, impaired sperm quality and testicular endocrine impairment with significant reduction in oxidative stress and unaltered body weight gain when compared with NaB-treated group.
Conclusion:
This study suggests that ascorbic acid and NaB synergistically aggravates testicular dysfunction. This is independent of oxidative stress status.
Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or spontaneously hypertensive rats (SHRs) is attenuated by increased central H2O2 concentration, produced either by direct H2O2 icv injection or by increased endogenous H2O2 centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280-330 g were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving SHRs. Acute intravenous injection of ATZ (300 mg/kg of body weight) did not modify MAP and HR during the next 4 h, however, the treatment with ATZ (300 mg/kg of body weight twice per day) for 3 days reduced MAP (144 ± 6, vs. saline, 183 ± 13 mmHg), without changing HR. Intravenous hexamethonium (ganglionic blocker) produced a smaller decrease in MAP 4 h after ATZ (-25 ± 3, vs saline -38 ± 4 mmHg). Losartan (angiotensinergic AT1 receptor blocker) produced a significant depressor response 4 h after ATZ (-22 ± 4, vs. saline: -2 ± 4 mmHg) and in 3-day ATZ treated SHRs (-25 ± 5, vs. saline: -9 ± 4 mmHg). The results suggest that the treatment with ATZ reduces sympathetic activity in SHRs and simultaneously increases angiotensinergic activity.
Conrad Waddington’s epigenetics landscape has provided a metaphorical framework
for how cells progress from undifferentiated states to one of several discrete, distinct,
differentiated cell fates. The understanding of epigenetics has evolved over time, with
DNA methylation being the most studied epigenetic modification, followed by histone
modifications and non-coding RNA.
Cardiovascular diseases (CVD) are leading contributors to death worldwide, with the prevalence of CVDs increasing across the last couple of decades. Significant amount of resources being poured into researching key mechanisms and underpinnings of the various CVDs. These molecular studies looked at the genetics, epigenetics as well as the transcriptomics of various cardiovascular conditions, aiming to provide mechanistic insights. It has paved the way for therapeutics to be developed and in recent years, epi-drugs for the treatment of CVDs. This chapter aims to cover the various roles of epigenetics in the context of cardiovascular health and disease. The following will be examined in detail: the developments in basic experimental techniques used to study epigenetics, the role of epigenetics in various CVDs (hypertension, atrial fibrillation, atherosclerosis, and heart failure), and current advances in epi-therapeutics, providing a holistic view of the current concerted efforts in advancing the field of epigenetics in CVDs.
Opuntia monacantha Haw. (Cactaceae) is a cochineal prickly pear with various medicinal uses. Its cladodes are consumed widely by local community in Mexico due its nutritional value and therapeutics effects. However, the cactus only known as an ornamental plant in Malaysia. To date, limited numbers of scientific studies have been conducted to explore its medicinal properties. Hence, the present study was carried out to evaluate the cytotoxicity and antioxidant of the cladodes of O. monacantha crude methanolic extract (MEOM), as well as phytoconstituents profiling. The cladodes of O. monacantha was extracted using maceration method with methanol in ratio (sample:methanol, 1:20L for 72hrs), followed by concentrated by means of rotary evaporator to obtain the crude methanol extract of the cladodes. Afterwards, the MEOM was tested for its toxicity using brine shrimp lethality test (BSLT), antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolics content (TPC) and total flavonoids content (TFC). Finally, chemical compounds were identified using UHPLC-Q-TOF/MS. According to Meyer and Clarkson toxicity criterion, the BSLT assay showed the extract possessed significant low toxicity LC50 of 1367.91 ppm. As for the antioxidant activity, the results exhibited that the extract could be categorized as having moderate antioxidant activity with IC50 value of 3.764 mg/mL DPPH activity, contain the TPC at 4.222±0.339 mg GAE/g extract, while no flavonoids were detected. According to the library of UHPLC-MS spectra, it has been identified the extract contain 22 potential active compounds from the cladodes of MEOM. The strongest peak identified as isoliquiritin, a flavonoid glycoside compound which possibly contribute to the moderate antioxidant activity. The findings are in agreement to the traditional uses of cladodes among natives in Mexico which were consumed safely and used for its various therapeutics values. Besides, the plant can be explored further as it has a potential to be developed into alternative-natural products in treating various discomforts and ailments with no side effects.
Two-thirds of US adults report hearing news stories about diet and health relationships daily or a few times a week. These stories have often been labeled as conflicting. While public opinion suggests conflicting nutrition messages are widespread, there has been limited empirical research to support this belief. This study examined the prevalence of conflicting information in online New York Times’ news articles discussing published nutrition research between 1996–2016. It also examined the contextual differences that existed between conflicting studies. The final sample included 375 news articles discussing 416 diet and health relationships (228 distinct relationships). The most popular dietary items discussed were alcoholic beverages (n = 51), vitamin D (n = 26), and B vitamins (n = 23). Over the 20-year study period, 12.7% of the 228 diet and health relationships had conflicting reports. Just under three-fourths of the conflicting reports involved changes in study design, 79% involved changes in study population, and 31% involved changes in industry funding. Conflicting nutrition messages can have negative cognitive and behavioral consequences for individuals. To help effectively address conflicting nutrition news coverage, a multi-pronged approach involving journalists, researchers, and news audiences is needed.
Introduction
The aim of this study was to describe functional and anatomical changes (best-corrected visual acuity [BCVA], central macular thickness [CMT], and central macular volume [CMV]) in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) treated with intravitreal dexamethasone implant (IDI) and identify its clinical predictors in a real-world setting.
Methods
Data from 111 patients who underwent IDI to treat RVO-associated ME were retrospectively reviewed. Demographic, preoperative, and postoperative variables were assessed using a logistic regression analysis to determine predictors of visual and anatomical improvement.
Results
Mean BCVA, CMT, and CMV improved from baseline after IDI ( p < 0.001). The strongest predictors of different treatment outcomes were: a baseline BCVA ⩽60 ETDRS letters (OR = 50.600; p < 0.001) and first IDI injection (OR = 2.988; p < 0.001) for BCVA gain ⩾15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; a baseline BCVA ⩽60 ETDRS letters (OR = 7.893; p = 0.002) and non-chronic ME (OR = 3.875; p = 0.019) for BCVA ⩾80 ETDRS letters achievement; a baseline CMT ⩾400 µm (OR = 49.083; p < 0.001) and a baseline CMV ⩾12 mm ³ (OR = 4.235; p < 0.001) for CMT reduction ⩾50%; and a baseline CMT ⩾400 µm (OR = 11.471; p < 0.001) and a baseline CMV ⩾12 mm ³ (OR = 10.284; p < 0.001) for CMV reduction ⩾15%.
Conclusion
This study confirmed the effectiveness of IDI to treat ME secondary to RVO and identified new predictive factors for two visual (⩾15 ETDRS letters gain and BCVA ⩾80 ETDRS letters) and two anatomical outcomes (>50% CMT and >15% CMV reduction).
Beyond the well-known effects on blood pressure (BP) of the DASH and the Mediterranean diets, a large number of studies have investigated the possible a BP-lowering effect from different dietary supplements and nutraceuticals, mostly antioxidant agents with a high tolerability and safety profile. In particular, a relatively large body of evidence support the use of potassium, L-arginine, vitamin C, cocoa flavonoids, coenzyme Q10, controlled-release melatonin, and aged garlic extract. However, there is a need for data about the long-term safety of a large part of these products. Moreover, further clinical research is advisable to identify between the available active nutraceuticals and those with the best cost-effectiveness and risk-benefit ratio for widespread use in a general population with low added cardiovascular risk related to uncomplicated hypertension.
Scope: Gut dysbiosis and dysregulation of the gut‐brain‐axis contributes to the pathogenesis of hypertension. Vitamin C (VC) is a common dietary supplement that shows the ability to lower the elevated blood pressure in hypertensive animals. Thus, we propose the hypothesis that the gut microbiota is involved in the anti‐hypertensive effect of VC.
Methods and results: We examined the changes of the gut microbiota and pathology in a spontaneously hypertensive rat (SHR) model after daily oral intake of VC in dosage of 200 mg/kg or 1000 mg/kg. After four weeks, the elevated blood pressure of SHRs in both VC‐treated groups were attenuated. Sequencing of the gut microbiota showed improvement in its diversity and abundance. Bioinformatic analysis suggested restored metabolism and biosynthesis related functions of the gut, which were confirmed by the improvement of gut pathology and integrity. Analysis of the hypothalamus paraventricular nucleus (PVN), the central pivot of blood pressure regulation, also showed reduced inflammatory responses and oxidative stress.
Conclusions: The reduced blood pressure, enriched gut microbiota, improved gut pathology and integrity, and reduced inflammatory responses and oxidative stress in the PVN together suggest that the anti‐hypertensive effects of VC involve reshaping of gut microbiota composition and function.
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Thirty six percent of people in USA and Canada regularly use complementary and alternative medicine (CAM) for the prevention and treatment of different diseases, including hypertension. Generally, majority of the hypertensive patients do not disclose the use of such remedies, and also health care providers do not usually ask their hypertensive patients if they use CAM. The widespread consumption of CAM in hypertension requires clear understanding of their underlying mechanism of action, efficacy and safety. This chapter will provide a comprehensive list of CAM commonly used by Americans for the prevention and treatment of hypertension as well as their postulated mechanism of action. Modulation of drug metabolizing enzymes and their safety will also be covered along with the clinical consequences, i.e. drug-herb or herb-disease interactions. patients and healthcare providers should also be careful with using CAM therapies, because not only is there minimal evidence that several CAM products work to treat hypertension, but their safety hasn't been well-established.
Intracerebroventricular (icv) injection of hydrogen peroxide (H2O2) or the increase of endogenous H2O2 centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with H2O2 injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5–10/group) with stainless steel cannulas implanted in the lateral ventricle were used. In freely moving rats, H2O2 (5 μmol/1 μl) or ATZ (5 nmol/1 μl) icv reduced the pressor responses to ANG II (50 ng/1 µl) icv in SHRs (11 ± 3 and 17 ± 4 mmHg, respectively, vs. 35 ± 6 mmHg) and 2K1C hypertensive rats (3 ± 1 and 16 ± 3 mmHg, respectively, vs. 26 ± 2 mmHg). ATZ (3.6 mmol/kg of body weight) iv alone or combined with H2O2 icv also reduced icv ANG II-induced pressor response in SHRs and 2K1C hypertensive rats. Baseline arterial pressure was also reduced (−10 to −15 mmHg) in 2K1C hypertensive rats treated with H2O2 icv and ATZ iv alone or combined and in SHRs treated with H2O2 icv alone or combined with ATZ iv. The results suggest that exogenous or endogenous H2O2 acting centrally produces anti-hypertensive effects impairing central pressor mechanisms activated by ANG II in SHRs or 2K1C hypertensive rats.
There is a trend for the rapid increase of the incidence of cardiovascular diseases. The age of disease initiation is getting younger, and the incidence is drastically increasing. Cardiovascular system consists of the heart and blood vessels. The heart acts as a pump that delivers two key substances for life, glucose and oxygen, to the cells. There are two kinds of vessels, arteries and veins. There are two clearly defined conditions for the formation of atherosclerotic lesions in the arterial endothelium. The first condition is micro-damage to the arterial endothelium. The second one is the peroxidation of cholesterol. Hypertension and diabetes mellitus (DM) are known to be the major causes of atherosclerotic vascular diseases. The significance of reactive oxygen species (ROS) generating during normal human metabolic processes for maintaining life cannot be overlooked. It can induce chronic endothelial damage over one’s life. Vitamin C can prevent LDL peroxidation by ROS as well as it can reduce endothelial damage to arteries. Vitamin C can also promote nitric oxide production, helpful in maintaining a normal range of blood pressure. There are two kinds of epidemiological studies on a relation between vitamin C and atherosclerotic vascular diseases; one is the study on a relation between the plasma vitamin C level and cardiovascular disease mortality and the other is the study on a relation between the amount of vitamin C intake and cardiovascular disease mortality. The former shows a clearer association between vitamin C and cardiovascular disease mortality than the latter. Exercise has so many advantages or benefits to maintain good health. However, exercise, especially aerobic ones, generate too much oxygen-free radicals. It is recommended to do aerobic exercise at 2–3 h after a meal with a regular intake of vitamin C.
Introducción: la hipertensión arterial (HTA) es una de las mayores cargas de enfermedad y riesgo para infarto cardíaco, la insuficiencia cardíaca y el fallo renal. Se reconoce que el estrés oxidativo (EO) es un determinante en el desarrollo de complicaciones y el progreso de la HTA. Se determinó el índice de EO (IEO) en individuos con HTA y en un grupo sano control, para evaluar su posible correlación.
Materiales y métodos: se midió IEO en una población de 112 individuos con HTA de distintos grados entre 50 y 70 años escogidos al azar y se comparó con los valores de un grupo control de voluntarios sanos, con la intención de definir el grado de correlación entre los niveles del IEO y la severidad de HTA, mediante la medición de biomarcadores para el EO en lisado de eritrocitos.
Resultados: a pesar de que los beneficios de la terapia antioxidante (TAO) no han sido definitivamente probadas, en gran parte porque las enfermedades complejas no dependen de un solo componente fisiopatogénico, el EO sigue siendo una piedra angular en el desarrollo de complicaciones y el empeoramiento de los cuadros clínicos de muchos padecimientos. La demostración de biomarcardores específicos mejora la posibilidad de una TAO dirigida. El presente ensayo demostró que la edad, el género y la etnia no influyen en el IEO y que el EO fue severo en los casos de HTA III, moderado en HTA II y estuvo ausente en el subgrupo con HTA grado I.
Conclusiones: estos resultados sugieren una relación entre los niveles de EO y severidad de HTA y sustenta evidencias para diseñar nuevos ensayos clínicos que evalúen la eficacia de una TAO adyuvante en el manejo de la HTA.
The excessive number of H⁺ or “:” and their asymmetrical distribution determines the performance of their surrounding water molecules in a way different from that of ordinary water. The naked lone pairs and protons are equally capable of interacting with the solvent H2O molecules to form O:H vdW bond, O:⇔:O super–HB or H↔H anti-HB without charge sharing or new bond forming. Solvation examination of alcohols, aldehydes, formic acids, and sugars reveals that O:H–O formation enables the solubility and hydrophilicity of alcohol; the H↔H anti-HB formation and interface structure distortion disrupt the hydration network and surface stress. The O:H phonon redshift depresses the freezing point of sugar solution of anti-icing.
Hypertensive nephropathy (HN) is a medical condition in which chronic high blood pressure causes different kidney damage, including vascular, glomerular and tubulointerstitial lesions. For HN patients, glomerular and tubulointerstitial lesions occur in different renal structure with distinct mechanisms in the progression of renal damage. As an extraction of Eucommia ulmoides, Quan-du-zhong capsule (QDZJN) has the potential to treat HN due to antihypertensive and renal protective activities. Complicated mechanism of HN underlying various renal lesions and the “multi-component and multi-target” characteristics of QDZJN make identifying drug positioning for various renal lesions of HN complex. Here, we proposed an approach based on drug perturbation of disease network robustness, that is used to assess QDZJN positioning for various HN lesions. Topological characteristics of drug-attacked nodes in disease network were used to evaluated nodes importance to network. To evaluate drug attack on the whole disease network of various HN lesions, the robustness of disease networks before/after drug attack were assessed and compared with null models generated from random networks. We found that potential targets of QDZJN were specifically expressed in the kidneys and tended to participate in the “inflammatory response,” “regulation of blood pressure,” and “response to LPS and hypoxia,” and they were also key factors of HN. Based on network robustness assessment, QDZJN may specifically target glomeruli account to the stronger influence on glomerular network after removal of its potential targets. This prediction strategy of drug positioning is suitable for multi-component drugs based on drug perturbation of disease network robustness for two renal compartments, glomeruli and tubules. A stronger influence on the disease network of glomeruli than of tubules indicated that QDZJN may specifically target glomerular lesion of HN patients and will provide more evidence for precise clinical application of QDZJN against HN. Drug positioning approach we proposed also provides a new strategy for predicting precise clinical use of multi-target drugs.
Aqueous charge injection in forms of electrons, protons, lone pairs, ions, and molecular dipoles by solvation is ubiquitously important to our health and life. Pursuing fine-resolution detection and consistent insight into solvation dynamics and solute capabilities has become an increasingly active subject. This treatise shows that charge injection by solvation mediates the O:H–O bonding network and properties of a solution through O:H formation, H↔H fragilization, O:⇔:O compression, electrostatic polarization, H2O dipolar shielding, solute–solute interaction, and undercoordinated H–O bond contraction. A combination of the hydrogen bond (O:H–O or HB with ‘:’ being the electron lone pairs of oxygen) cooperativity notion and the differential phonon spectrometrics (DPS) has enabled quantitative information on the following: (i) the number fraction and phonon stiffness of HBs transiting from the mode of ordinary water to hydration; (ii) solute–solvent and solute–solute molecular nonbond interactions; and (iii) interdependence of skin stress, solution viscosity, molecular diffusivity, solvation thermodynamics, and critical pressures and temperatures for phase transitions. An examination of solvation dynamics has clarified the following: (i) the excessive protons create the H↔H or anti-HB point breaker to disrupt the acidic solution network and surface stress. (ii) The excessive lone pairs generate the O:⇔:O or super–HB point compressor to shorten the O:H nonbond but lengthen the H–O bond in H2O2 and basic solutions; yet, bond-order-deficiency shortens and stiffens the H–O bond due H2O2 and OH⁻ solutes. (iii) Ions serve each as a charge center that aligns, clusters, stretches, and polarizes their neighboring HBs to form hydration shells. (iv) Solvation of alcohols, aldehydes, complex salts, carboxylic and formic acids, glycine, and sugars distorts the solute–solvent interface structures with the involvement of the anti-HB or the super-HB. Extending the knowledge and strategies to catalysis, solution–protein, drug–cell, liquid–solid, colloid–matrix interactions and molecular crystals would be even more fascinating and rewarding.
Cardiovascular disease is the greatest cause of mortality in developed countries and diet plays an important role in contributing to the development and progression of ischemic heart disease (IHD). The influences of general nutrition and micronutrients such as vitamins and minerals on the progression of IHD are poorly understood and recent studies have done little to clarify the situation.
L-Ascorbic acid (AA) or vitamin C is a six carbon cetolactone, structurally related to glucose and other hexoses. The major sources of AA are citrus fruits, strawberry, melon, green pepper, potato, tomato and leafy green vegetables. AA interferes with a broad spectrum of oxidation-reduction reactions, acting in at least 10 enzymatic systems. In this way, vitamin C influences the synthesis of collagen, carnitine, and neurotransmitters; the transformation of cholesterol into bile acids; biotransformation of xenobiotics substances; absorption of iron; and formation and scavenging of oxygen free radicals. AA is used as food addictive because of its antioxidant properties.Therapeutically, it is used as nutritional supplement during scurvy. Human beings and other primates, as well as guinea pigs and some species of bats are mammals that are unable to synthesize AA; thus, they need AA in the diet to prevent scurvy. Rats are able to synthesize AA using glucose, through intermediary formation of D-glucuronic acid, L-gulonic acid and gulonolactone.Homo sapiens lack the hepatic enzyme gulonolactone oxidase, which catalyses the last reaction of the biosynthesis pathway (L-gulonolactone conversion to ascorbic acid). The functions of central nervous, immune, and cardiovascular systems, and the periodontal tissue, as well as the detoxification function of the liver, are negatively influenced by vitamin C deficiency. In this way, it has been described several benefits of vitamin supplement ingestion, as decreasing of LDL cholesterol, including mega doses that can reach as much as 18g daily. Although there have been raised many literatures about vitamin C use in a wide variety of diseases, there is a lack of clinical efficiency of mega doses; besides, some side effects can come up, as diarrhea and oxalate stones in the kidneys. However, the ideal daily intake of vitamin C is still unknown. This happen because the recommended daily intake is based in a single role of AA, the scurvy prevention. Daily ingestion of AA should be the same quantity excreted or destroyed by oxidation, taking into consideration AA actions on the enzymatic systems. Actually, vitamin C is necessary for health in little quantities and is harmful in large doses. It happens because the cells are always walking a balance between oxidation and reduction processes, and AA in great quantities assume oxidative characteristics, interfering in this balance. Although the existence of several evidences indicating AA toxicity in large doses, there are some authors who believe that the ingestion of large doses is safe, but they admit that the disposable data are very contradictory.
We investigated the association of dietary fatty acids and antioxidants with blood pressure in 722 eastern Finnish men aged 54 y, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-86. Men with self-reported hypertension or cerebrovascular disease or under antihypertensive medication were excluded. Allowing for the major anthropometric, dietary, medical, and psychological determinants of blood pressure in multivariate regression analyses, both plasma ascorbic acid (p = 0.0008) and serum selenium (p = 0.0017) concentrations had a moderate, independent inverse association, estimated dietary intake of saturated fatty acids had a positive association (p = 0.013), and estimated dietary intake of linolenic acid had an inverse (p = 0.048) association with the mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma ascorbic acid and serum Se concentrations supports the hypothesis that antioxidants play a role in the etiology of hypertension.
We examined the relation between vitamin C intake and mortality in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study cohort. This cohort is based on a representative sample of 11,348 noninstitutionalized U.S. adults age 25-74 years who were nutritionally examined during 1971-1974 and followed up for mortality (1,809 deaths) through 1984, a median of 10 years. An index of vitamin C intake has been formed from detailed dietary measurements and use of vitamin supplements. The relation of the standardized mortality ratio (SMR) for all causes of death to increasing vitamin C intake is strongly inverse for males and weakly inverse for females. Among those with the highest vitamin C intake, males have an SMR (95% confidence interval) of 0.65 (0.52-0.80) for all causes, 0.78 (0.50-1.17) for all cancers, and 0.58 (0.41-0.78) for all cardiovascular diseases; females have an SMR of 0.90 (0.74-1.09) for all causes, 0.86 (0.55-1.27) for all cancers, and 0.75 (0.55-0.99) for all cardiovascular diseases. Comparisons are made relative to all U.S. whites, for whom the SMR is defined to be 1.00. There is no clear relation for individual cancer sites, except possibly an inverse relation for esophagus and stomach cancer among males. The relation with all causes of death among males remains after adjustment for age, sex, and 10 potentially confounding variables (including cigarette smoking, education, race, and disease history).
Although active oxygen species play important roles in the pathogenesis of various diseases, the molecular mechanism for oxygen toxicity in vascular diseases remains to be elucidated. Since endothelium-derived relaxing factor (EDRF) is inactivated by superoxide radicals in vitro, oxidative stress in and around vascular endothelial cells may affect the circulatory status of animals. To study the role of superoxide radicals and related enzymes, such as superoxide dismutase (SOD), in vascular diseases, we have developed a fusion protein (HB-SOD) consisting of human Cu/Zn-type SOD and a C-terminal basic peptide with high affinity for heparan sulfate on endothelial cells. When injected intravenously, HB-SOD bound to vascular endothelial cells, underwent transcellular transport, and localized within vascular walls by a heparin-inhibitable mechanism. The blood pressure of spontaneously hypertensive rats (SHR) but not normal animals was decreased significantly by HB-SOD. Heparin inhibited the depressor effect of HB-SOD. In contrast, native SOD had no effect on blood pressure of either SHR or normal rats. Neither H2O2-inactivated HB-SOD nor the C-terminal heparin-binding peptide showed such a depressor effect, suggesting that the catalytic function of HB-SOD is responsible for its depressor action. To know the source of superoxide radicals, we determined xanthine oxidase activity in the aorta and uric acid levels in the plasma. Although no appreciable difference in xanthine oxidase activity was found between the two animal groups, uric acid levels were significantly higher in SHR than in normal rats. Oxypurinol, a potent inhibitor of xanthine oxidase, also decreased the blood pressure of SHR but not of normal rats. These findings indicate that superoxide radicals in and around vascular endothelial cells play critical roles in the pathogenesis of hypertension of SHR.
1. Hypertension affects 30% of adults and low intakes of antioxidants have been associated with increased risk of hypertension and cardiovascular disease. To investigate the effect of short-term high-dose antioxidant supplementation on blood pressure in hypertensive and normotensive outpatients, we undertook a randomized, double-blind, crossover design placebo-controlled study.
2. Forty subjects were recruited from medical outpatient clinics, of whom 38 completed the study. Twenty-one were attending for treatment of hypertension and 17 were normotensive, attending for minor gastrointestinal complaints. Subjects were randomly assigned to receive either 8 weeks placebo followed by 2 weeks washout then 8 weeks antioxidants or vice versa. The combination of antioxidants consisted of 200 mg of zinc sulphate, 500 mg of ascorbic acid, 600 mg of α-tocopherol (sodium succinate salt) and 30 mg of β-carotene daily.
3. Systolic blood pressure fell at the end of the antioxidant phase compared with the placebo phase both in subjects receiving anti-hypertensive therapy (P < 0.01) and those who were normotensive (P = 0.067). Circulating levels of β-carotene and α-tocopherol increased in all subjects during supplementation (P < 0.01) and urine nitrite increased in hypertensive patients (P < 0.05).
4. Short-term oral high-dose combination antioxidant therapy reduces blood pressure, possibly via increased availability of nitric oxide. This study may have implications for the innovative use of antioxidants as an adjunct to anti-hypertensive therapy.
Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients.
In 14 healthy subjects (47.1+/-4.8 years; blood pressure, 120.6+/-4.5/80.9+/-3.5 mm Hg) and 14 essential hypertensive patients (47.3+/-5.1 years; blood pressure, 153.9+/-7.1/102.3+/-4.1 mm Hg), we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg x 100 mL(-1) x min(-1)) or sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute), an endothelium-dependent and -independent vasodilator, respectively, in basal conditions and during infusion of intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). In hypertensive patients but not in control subjects, vitamin C increased (P<0.01) the impaired vasodilation to acetylcholine, whereas the response to sodium nitroprusside was unaffected. Moreover, in another 14 hypertensive patients (47.1+/-5.2 years; blood pressure, 155.2+/-6.9/103.7+/-4.5 mm Hg), the facilitating effect of vitamin C on vasodilation to acetylcholine was reversed by N(G)-monomethyl-L-arginine (100 microg/100 mL forearm tissue per minute), a nitric oxide synthase inhibitor, suggesting that in essential hypertension superoxide anions impair endothelium-dependent vasodilation by nitric oxide breakdown. Finally, because in adjunctive 7 hypertensive patients (47.8+/-6.1 years; blood pressure, 155.3+/-6.8/103.5+/-4.3 mm Hg), indomethacin (50 microg/100 mL forearm tissue per minute), a cyclooxygenase inhibitor, prevented the potentiating effect of vitamin C on vasodilation to acetylcholine, it is possible that in essential hypertension a main source of superoxide anions could be the cyclooxygenase pathway.
In essential hypertensive patients, impaired endothelial vasodilation can be improved by the antioxidant vitamin C, an effect that can be reversed by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine. These findings support the hypothesis that nitric oxide inactivation by oxygen free radicals contributes to endothelial dysfunction in essential hypertension.
Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension.
- Taddei S
- Virdis A
- Qhiadoni L
- Magagna A
- Salvetti A