Role of nNOS in cardiac ischemia-reperfusion injury

Recent studies have consistently demonstrated that neuronal nitric oxide synthase (nNOS) is cardioprotective in different disease states. nNOS has been shown to delay transition to heart failure in response to pressure overload, to protect the myocardium from functional deterioration after myocardial infarction, and to decrease mortality after myocardial infarction. Recent work identified the precise molecular mechanisms of nNOS action in the myocardium during rest and after myocardial damage. In animal models with nNOS overexpression restricted to cardiac myocytes and nNOS(-/-) mice, it was consistently demonstrated that nNOS decreased myocardial contractility via inhibition of the I(Ca,L) amplitude and [Ca(2+)](i) transients. The mitochondria and xanthine oxidoreductase were identified as further targets for nNOS in cardiac disease models. In this review, we focus on the protective effects of nNOS after ischemia-reperfusion injury, with emphasis on the subcellular localization of nNOS and its putative targets.