INVOLVEMENT OF INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE INFLAMMATORY PROCESS OF MYOCARDIAL

Inducible nitric oxide synthase (iNOS), which catalyzes the reaction o f L-arginine to L-citrulline and nitric oxide (NO), plays an important role in immune-mediated cardiac disorders. The present report summari zes and discusses findings on the induction of NOS in myocardial infar ction of rabbits. iNOS was significantly increased in infarcted myocar dium 48 h after coronary artery ligation. The effect persisted for 14 days and declined thereafter. Immunohistochemcial localization reveale d macrophages as a major source of iNOS expression; iNOS expression wa s also present in infarcted human myocardium. Increased iNOS activity appeared to be related to the induction of apoptosis in infiltrating m acrophages and cardiomyocytes. Moreover, preferential inhibition of iN OS by S-methylisothiourea sulfate (SMT) resulted in significant improv ement of left ventricular performance and increased regional myocardia l blood flow. These findings suggest that selective inhibition of iNOS activity may provide a therapeutic strategy in cardiac disorders such as myocardial infarction.