Glutathione Protects Against Myocardial Ischemia–reperfusion Injury by Detoxifying Peroxynitrite

Abstract

P.-Y. Cheung, W. Wang and R. Schulz. Glutathione Protects Against Myocardial Ischemia–reperfusion Injury by Detoxifying Peroxynitrite. Journal of Molecular and Cellular Cardiology (2000) 32, 1669–1678. Peroxynitrite (ONOO−) formation during acute reperfusion of the ischemic heart contributes to the poor recovery of mechanical function. As glutathione (GSH) detoxifies ONOO−, we studied whether it could protect isolated rat hearts subjected to exogenous ONOO−or to ischemia–reperfusion. We showed that GSH (300 μ m,n =5) abolished the detrimental effect of ONOO−(80 μ m, n=5) on mechanical function of aerobically perfused hearts. Hearts were subjected to 25 min aerobic perfusion, 20 min global, no-flow ischemia and 30 min reperfusion. GSH (3–300 μ m, n=7–12) or saline vehicle (control,n =22) were infused for 10 min prior to ischemia and throughout reperfusion. During reperfusion, GSH caused a concentration-dependent improvement in the recovery of mechanical function, which was not associated with significant changes in the intracellular concentration of GSH. The concentration of dityrosine (a marker of ONOO−formation) in the coronary effluent during reperfusion was significantly reduced in GSH-treated hearts. The concentration of myocardial cGMP was significantly elevated by GSH during ischemia and early reperfusion. GSH improves the recovery of myocardial mechanical function after ischemia–reperfusion, an effect which may be related to the detoxification of ONOO−by GSH and the stimulation of soluble guanylate cyclase.