Cardiomyocyte-specific overexpression of nitric oxide synthase 3: impact on left ventricular function and myocardial infarction.

Identification of all three nitric oxide (NO) synthase (NOS) isoforms in cardiac myocytes and the recognition of the importance of their subcellular localization have greatly advanced the understanding of the critical role of NO signaling in myocardial function. Targeted deletion of endothelial NOS (NOS3) has revealed a fundamental role for this NOS isoform in the structural and functional responses of the heart to pressure and volume overload. The recent generation of transgenic models with overexpression of NOS3 restricted to the cardiac myocyte has enabled a unique appreciation of the ability of NO to modulate cardiac muscle, independent of changes in cardiac loading conditions. Consistent with the targeting of overexpressed NOS3 to caveolae in the vicinity of cholinergic and adrenergic receptors, these studies have highlighted the importance of NOS3-derived NO in the modulation of autonomic cardiac stimulation. In vivo models of myocardial infarction suggest that NOS3 overexpression can limit compensatory hypertrophy in the remote myocardium and preserve left ventricular performance. Development of therapeutic strategies designed to enhance NO signaling in cardiac myocytes may target maladaptive left ventricular remodeling and improve functional recovery after myocardial infarction.