Involvement of inducible nitric oxide synthase in the inflammatory process of myocardial infarction.

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