S-nitrosoglutathione preserves vasodilation and attenuates myocardial ischemia-reperfusion injury.

Abstract

Ischemia/reperfusion (I/R) injury exacerbates myocardial damage following acute myocardial infarction, underscoring the need for effective cardioprotective therapies. S-nitrosoglutathione (GSNO), an endogenous S-nitrosothiol, functions as a nitric oxide (NO) reservoir with vasodilatory and cytoprotective properties; however, its therapeutic potential in myocardial I/R injury remains incompletely characterized. We hypothesized that GSNO protects against I/R-induced cardiac injury by improving coronary vasodilation. The effects of GSNO were evaluated in an isolated Wistar rat heart model of regional ischemia followed by reperfusion using the Langendorff system. Reperfusion with GSNO-containing buffer (200 µM and 500 µM) enhanced coronary perfusion; however, only GSNO at 200 µM significantly reduced infarct size. GSNO also induced concentration-dependent relaxation in isolated coronary artery rings, confirming its potent vasodilatory activity. In vitro assays exposing cardiomyoblasts and endothelial cells to increasing GSNO concentrations revealed greater susceptibility of cardiomyoblasts to GSNO-induced cytotoxicity. Collectively, these findings demonstrate a dose-dependent cardioprotective effect of GSNO, likely mediated by sustained NO bioavailability and enhanced coronary vasodilation. This study supports GSNO as a promising NO-based adjunct therapy for mitigating myocardial I/R injury and provides important insights for optimizing its dosing strategy toward clinical translation.