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[Effects of continuous adenosine infusion on pulmonary hypertension in chronically hypoxic rats]
Abstract
To observe the effects of continuous subcutaneous adenosine infusion on pulmonary hypertension in chronically hypoxic rats.
Twenty-four SD rats were randomized into normoxic group, hypoxic group and adenosine-treated hypoxic group. Hypoxic environment was simulated in a chamber filled with 10% oxygen and 90% nitrogen. After 7 days of hypoxia, adenosine were administered subcutaneously in the rats in adenosine-treated group at the rate of 100 microg kg(-1) min(-1) via an Alzet micro-osmotic pump for 14 days, while the pumps in the other two groups contained normal saline. After 21 days of hypoxia, pulmonary artery pressure and tail-cuff blood pressure were measured, with the plasma rennin activity (RA), angiotensin II (AngII), endothelin (ET)-1, and nitric oxide (NO) determined. Inducible nitric oxide synthase (iNOS) expression in the pulmonary artery of the rats was detected using immunohistochemical method.
The mean pulmonary artery pressure (mPAP) was significantly higher in the hypoxic group than that in the normoxic group (P<0.01) and in the adenosine-treated group (P<0.01). Plasma ET-1 was significantly higher but plasma NO significantly lower in the hypoxic group than in the normoxic group (P<0.01) and the adenosine-treated group (P<0.01). iNOS expression in the pulmonary artery was higher in the hypoxic group than in normoxic group (P<0.01), and adenosine significantly increased iNOS expression in comparison with the normoxic and hypoxic groups (P<0.01). Plasma RA and AngII in the hypoxic group were significantly higher than those in the normoxic group (P<0.01) and the adenosine-treated (P<0.01).
Adenosine administered by continuous subcutaneous infusion alleviates chronically hypoxia-induced pulmonary hypertension in rats, in which rennin angiotensin system, ET-1, and iNOS/NO play a role.
... It is reported that adenosine deaminase maintains a high level of activity, and the production of adenosine increases significantly in the early stage of hypoxia. After adapting to hypoxia, the production of adenosine decreases, so that the metabolic rate of adenosine exceeds its production rate [32]. In addition, adenosine is constantly consumed due to its binding with receptor, which may be the reason for the decrease of adenosine in plasma. ...
When ascending to high altitude, it is a rigorous challenge to people who living in the low altitude area to acclimatize to hypoxic environment. Hypoxia exposure can cause dramatic disturbances of metabolism. This longitudinal cohort study was conducted to delineate the plasma metabolomics profile following exposure to altitude environments and explore potential metabolic changes after return to low altitude area. 25 healthy volunteers living in the low altitude area (Nor; 40m) were transported to high altitude (HA; 3,650m) for a 7-day sojourn before transported back to the low altitude area (HAP; 40m). Plasma samples were collected on the day before ascending to HA, the third day on HA(day 3) and the fourteenth day after returning to low altitude(14 day) and analyzed using UHPLC-MS/MS tools and then the data were subjected to multivariate statistical analyses. There were 737 metabolites were obtained in plasma samples with 133 significantly changed metabolites. We screened 13 differential metabolites that were significantly changed under hypoxia exposure; enriched metabolic pathways under hypoxia exposure including tryptophan metabolism, purine metabolism, regulation of lipolysis in adipocytes; We verified and relatively quantified eight targeted candidate metabolites including adenosine, guanosine, inosine, xanthurenic acid, 5-oxo-ETE, raffinose, indole-3-acetic acid and biotin for the Nor and HA group. Most of the metabolites recovered when returning to the low altitude area, however, there were still 6 metabolites that were affected by hypoxia exposure. It is apparent that high-altitude exposure alters the metabolic characteristics and two weeks after returning to the low altitude area a small portion of metabolites was still affected by high-altitude exposure, which indicated that high-altitude exposure had a long-term impact on metabolism. This present longitudinal cohort study demonstrated that metabolomics can be a useful tool to monitor metabolic changes exposed to high altitude, providing new insight in the attendant health problem that occur in response to high altitude.
Our previous study found that Chinese chive could significantly (p < 0.01) raise testosterone and nitric oxide (NO) levels in mice serum. However, the specific functional components of this traditional remedy are still unknown. In order to isolate and identify the active constituents from Chinese chive for enhancing testosterone and NO levels, the Chinese chive leaves were extracted by petroleum ether, ethyl acetate, n‐butanol and water respectively. Results indicated that the n‐butanol extract had a significant effect on NO and testosterone blood levels. Subsequently, n‐butanol extract was further isolated by D101 macroporous adsorption and eluted with 50% ethanol and then isolated by Sephadex LH‐20 and preparative high‐performance liquid chromatography to obtain nucleosides. The fraction eluted with 70% ethanol was further isolated by RP‐18 and pre‐HPLC to obtain nucleotides. Four novel compounds were identified, and their effects on testosterone and NO levels of male mice were evaluated. Results showed that nucleotides, especially the adenosine in Chinese chive leaves, increased serum testosterone and NO levels in male mice, which had not been reported before. This finding might bring into perspective the treatment strategy for those doctors who treat hormone deficiencies, and might be suitable for using in functional food.
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