Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase

Myocardial ischemia and reperfusion (MI/R) initiates a cascade of polymorph onuclear neutrophil (PMN)-mediated injury, the magnitude of which may be in fluenced by the bioavailability of nitric oxide (NO). We investigated the r ole of endothelial cell nitric oxide synthase (ecNOS) in MI/R injury by sub jecting wild-type and ecNOS-deficient (-/-) mice to 20 min of coronary arte ry occlusion and 120 min of reperfusion. Myocardial infarct size represente d 20.9 +/- 2.9% of the ischemic zone in wild-type mice, whereas the ecNOS - /- mice had significantly (P < 0.01) larger infarcts measuring 46.0 +/- 3.8 % of the ischemic zone. Because P-selectin is thought to be involved with t he pathogenesis of neutrophil-mediated I/R injury, we assessed the effects of MYR on P-selectin expression in the myocardium of wild-type and ecNOS -/ - mice. P-selectin expression measured with a radiolabeled monoclonal antib ody (MAb) technique after MI/R in wild-type mice was 0.037 +/- 0.009 mu g M Ab/g tissue, whereas ecNOS -/- coronary vasculature was characterized by si gnificantly (P < 0.05) higher P-selectin expression (0.080 +/- 0.013 mu g M Ab/g tissue). Histological examination of the postischemic myocardium revea led significantly (P < 0.01) more neutrophils in the ecNOS -/- (29.5 +/- 2. 5 PMN/field) compared with wild-type (5.0 +/- 0.9 PMN/field) mice. A simila r trend in infarct size and neutrophil accumulation was observed when wild- type and ecNOS -/- mice were subjected to 30 min of ischemia and 120 min of reperfusion. These novel in vivo findings demonstrate a cardioprotective r ole for ecNOS-derived NO in the ischemic-reperfused mouse heart.