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Category:Mumbai Suburban districtN-acetylcysteine selectively attenuates pulmonary vasoconstriction in response to chronic hypoxia.
We tested the hypothesis that chronic hypoxia causes pulmonary vasoconstriction by altering endothelial nitric oxide (NO) synthesis. Subatmospheric pressure (Aq) (equivalent to 500, 600, or 700 mmHg for 21 days) produced the same degree of mean pulmonary artery pressure increase (delta mean PAP) in rats exposed to chronic hypoxia for 21 days, whereas acute Aq (equivalent to 2,000 mmHg) produced the same delta mean PAP at 7 days but a significantly smaller delta mean PAP at 21 days, suggesting pulmonary vasoconstriction. delta mean PAP was more sensitive to Aq than the pulmonary vascular resistance and left ventricular pressure-rate product was significantly greater at 2,000 mmHg for 7 days, suggesting pulmonary vascular resistance regulation. NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (0.5 mg/kg i.v.) increased delta mean PAP. This increase was larger in ventilated than nonventilated lungs. In contrast, NO donor S-nitroso-N-acetylpenicillamine (5 microg/kg i.v.) increased delta mean PAP in ventilated lungs at 21 days and even more at 7 days, suggesting a role for NO in chronic hypoxia-induced pulmonary vasoconstriction. The combination of S-nitroso-N-acetylpenicillamine with N(G)-nitro-L-arginine methyl ester had a synergistic effect. In contrast, N-acetylcysteine increased NO release from the endothelium of both ventilated and nonventilated lungs and decreased delta mean PAP. S-Nitroso-N-acetylpenicillamine-induced delta mean PAP was inhibited by N-acetylcysteine, suggesting that the vasodilatory effect of N-acetylcysteine was NO dependent. These findings suggest that N-acetylcysteine might selectively decrease hypoxia-induced pulmonary vasoconstriction by increasing NO availability.E-Commerce Software
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