l-Arginine limits myocardial cell death secondary to hypoxia-reoxygenation by a cGMP-dependent mechanism

Abstract

The objective of this study was to investigate the effect ofl-arginine supplementation on myocardial cell death secondary to hypoxia-reoxygenation. Isolated rat hearts ( n = 51) subjected to 40 min of hypoxia and 90 min of reoxygenation received 3 mMl-arginine and/or 1 μM 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (ODQ; a selective inhibitor of soluble guanylyl cyclase) throughout the experiment or during the equilibration, hypoxia, or reoxygenation periods. The incorporation ofl-[3H]arginine into myocytes during energy deprivation was investigated in isolated adult rat myocytes. The addition ofl-arginine to the perfusate throughout the experiment resulted in higher cGMP release ( P < 0.05), reduced lactate dehydrogenase release ( P < 0.05), and increased pressure-rate product ( P < 0.05) during reoxygenation. These effects were reproduced whenl-arginine was added only during equilibration, but addition ofl-arginine during hypoxia or reoxygenation had no effect. Addition of ODQ either throughout the experiment or only during reoxygenation reversed the beneficial effects of l-arginine.l-[3H]arginine was not significantly incorporated into isolated myocytes subjected to energy deprivation. We conclude thatl-arginine supplementation protects the myocardium against reoxygenation injury by cGMP-mediated actions. To be effective during reoxygenation,l-arginine must be added before anoxia.