Heart Mitochondrial Nitric Oxide Synthase: A Strategic Enzyme in the Regulation of Cellular Bioenergetics

Abstract

Heart mitochondria play a central role in cell energy provision and in signaling. Nitric oxide (NO) is a free radical which exerts an integral regulation of the cardiovascular system not only by adapting vascular smooth muscle tone but also by influencing ion channel function, myocyte contraction, energy metabolism, and hypertrophic myocardial remodeling. This chapter analyzes the available data about heart mitochondrial NOS (mtNOS) activity and identity. The regulation of heart mtNOS by the distinctive mitochondrial environment is described by showing the effects of Ca2+, O2, L-arginine NADPH, mitochondrial membrane potential (ΔΨ) and the metabolic states. Evidence about the regulation of heart mtNOS in chronic hypoxia and ischemia?reperfusion models is presented. Functional implications of heart mitochondrial NOS are delineated with emphasis on the chemical reactions through which NO interacts with mitochondrial targets and exerts some of its crucial roles.