The cardiovascular effects and implications of peroxynitrite

Nitric oxide is an endogenous autacoid produced primarily by the vascular endothelium. Under basal conditions, nitric oxide undergoes a rapid biradical reaction with superoxide anions to form peroxynitrite. This reaction, and hence the formation of peroxynitrite is augmented in inflammatory-like conditions such as ischemia-reperfusion injury when both substrates are present in high concentrations. Peroxynitrite has been implicated as a physiologically active toxic metabolite of nitric oxide leading to vascular and myocardial dysfunction. Recent evidence, however, has suggested that peroxynitrite may actually have beneficial properties under in vivo biological conditions when thiol-containing agents (glutathione, albumin, cysteine) agents are available to convert the peroxynitrite anion to nitrosothiols and related products demonstrating antineutrophil and cardioprotective properties. The dichotomy of physiologically relevant properties of peroxynitrite has important clinical applications with respect to nitric oxide therapy for cardiac, vascular, cerebral and pulmonary disease states. This review summarizes the biological properties of peroxynitrite relevant to the cardiovascular system.