Effect of redox agents on the response of rat aorta to nitric oxide and sodium nitroprusside

Abstract

Objective: To study the redox regulation of vascular responses to endogenous nitric oxide (NO) and NO derived from nitrovasodilator sodium nitroprusside (SNP) in isolated rat aorta. Materials and Methods: To determine the influence of reducing [ascorbic acid (1 mM) and reduced glutathione (GSH) (1 mM)] and oxidizing agents [oxidized glutathione (GSSG) (1 mM) and CuSO4 (1 and 5 µM)] on the vasodilation caused by acetylcholine (ACh; 10-11-10-5 M) and SNP (10-9-10-4 M). Isometric tensions were measured in isolated aorta by a force transducer and recorded in a computer, using Chart V4.1.2 software. Results: ACh and SNP produced relaxation of rat aortic rings that was dependent on concentration. The rings were preconstricted with L-phenylephrine (1 µM). It was observed that oxidizing and reducing agents caused opposite effects on vasodilation induced by NO in rat aorta. Ascorbic acid and GSH potentiated the responses to NO, causing a leftward shift in the concentration-response curve of ACh with significant increase in the pD2 and the Emax. GSSG and CuSO4 inhibited relaxation caused by ACh and shifted the concentration-response curve to the right. In concentration-responses induced by SNP, ascorbic acid significantly increased the pD2 and Emax values from 5.85 ± 0.08 to 6.24 ± 0.05 and 80.83 ± 1.37% to 89.26 ± 1.49%, respectively. However, CuSO4 significantly decreased these values from 5.85 ± 0.02 to 4.56 ± 0.10 and 77.18 ± 0.82% to 53.52 ± 1.60%, respectively. Potentiation of NO response by reducing agents may be related to either increased availability of nitroxyl anion (NO-) or reduction in superoxide anion radical (O2·-). The opposite could be true for the oxidizing agents. Conclusion: The findings of this study suggest that reducing agents like ascorbic acid can improve the vascular responses to NO under oxidative stress.