The assessment of the relaxant effect of S-nitrosoglutathione on isolated human saphenous vein

Abstract

S-nitrosothiols (RSNOs) are thought to represent the circulating reservoir of nitric oxide (NO). S-nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol which suggested to be a potent vasodilator with a prolonged relaxant effect compared to the current NO donors that clinically used. There are limited studies about its vascular effects on human vessels while no data is available on its mechanism of action. In this study, we aimed to investigate the acute effect of GSNO on human saphenous vein rings as well as the possible underlying mechanisms. Isolated human saphenous veins obtained from coronary artery bypass surgery, were mounted in an organ bath system, aerated with %5CO2 + %95o 2 at 37o C with a resting tension of 2g. The effect of GSNO (10-8 -10-4 M) were studied in a concentration-dependent manner on rings precontracted submaximally with phenylephrine (3x10-5 M). In order to analyse its mechanism of action, the effects of GSNO were studied in the absence and presence of NO synthase inhibitor, L-NAME (10-4 M, 30min), soluble guanylyl cyclase (sGC) inhibitor, ODQ (10-5 M, 30min) or a selective inhibitor of ATP-sensitive K+ channels (KATP), glibenclamide (10-5 M, 30min). GSNO produced concentration-dependent relaxant effects on precontracted human saphenous veins (Emax: 102,40±1,37%). The prominent relaxant influence of GSNO was not altered in the presence of the inhibitor of NO synthase or KATP channels. While, a significant decrease was observed with ODQ (ODQ-Emax: 43,73±8,61%; Control-Emax:108,4±4,76%, p<0.001, n=5) Our results indicate that acute relaxant effects of GSNO in isolated human saphenous vein were neither mediated by KATP channel activation nor endogenous NO. Whereas, the activation of sGC pathway is likely be involved in this response. A better understanding of the mechanism regulating the vasorelaxant effect of GSNO and its possible role as a new antispasmodic agent for bypass graft spasms will provide us new therapeutic opportunities. Keywords: S-nitrosoglutathione, nitric oxide, coronary artery bypass graft, human saphenous vein