Myocardial reperfusion injury in neuronal nitric oxide synthase deficient mice

Abstract

A substantial amount of data suggesting that endothelial cell nitric oxide synthase (eNOS) plays a cardioprotective role in animal models of ischemia-reperfusion injury has amassed. We have previously demonstrated that eNOS-deficient (-/-) mice exhibit significantly larger myocardial infarcts than do wild-type mice. Few investigations have examined the neuronal form of nitric oxide synthase in the heart. The two constitutive isoforms have been demonstrated to play differing roles in studies of cerebral ischemia-reperfusion. To characterize the role of neuronal nitric oxide synthase (nNOS) in myocardial ischemia-reperfusion injury. Wild-type and nNOS -/- mice were subjected to 20 min of coronary artery occlusion and 120 min of reflow. We found no significant difference between the two groups in terms of infarct size. Microscopic cross-sections from both groups were examined for infiltration of polymorphonuclear leukocyte. Hearts of nNOS -/- mice exhibited significantly (P < 0.05) more polymorphonuclear leukocytes than did hearts of wild-type mice. Despite the fact that eNOS plays a cardioprotective role in the ischemic-reperfused myocardium, we observed no change in size of myocardial infarcts when nNOS was genetically disrupted.