Reactive oxygen species and nitric oxide in myocardial ischemia and reperfusion

Oxygen radicals and reactive oxygen species (ROS) are known to be generated in large amounts under inflammatory conditions and in the first few minute s of postischemic organ reperfusion. Due to the interaction of ROS with nit ric oxide (NO), formed constitutively by endothelial cells, two alternative s are feasible. On the one hand, reaction with superoxide radicals may indu ce toxification (formation of peroxynitrite), and, on the other hand, by re acting with superoxide and hydroxyl radicals, NO can serve as a radical sca venger (formation of the innocuous anions, nitrate and nitrite, respectivel y). However, NO is considered to play a pivotal role in numerous physiologi cal and pathophysiological processes, with effects arising from both lack a nd surfeit of this easily diffusible and chemically very reactive molecule. Physiologic contributions to vascular dilatation and inhibition of platele t and leukocyte activation, e.g., are infringed by enhanced inactivation of NO. Such inactivation occurs readily due to spontaneous reaction of NO wit h the superoxide radical, formed, e.g., by stressed endothelial cells and a ctivated leukocytes. Conversely, overproduction of NO by induced NO synthas e (iNOS) may lead to circulatory shock, cell apoptosis or even cell necrosi s. Caution would, thus, seem to be warranted when attempting to interfere w ith homeostasis of NO. We have investigated the ability of NO to act as a r adical scavenger during myocardial reperfusion in experimental and clinical settings. In the former, inhibition of angiotensin converting enzyme was e mployed to generate more endogenous NO (via bradykinin), in the latter, low -dose sodium nitroprusside was used as the donor of exogenous NO in patient s undergoing coronary bypass grafting. Inhibition of leukocyte adhesion, at tenuation of platelet activation and mitigation of redox-stress and inflamm ation were observed in both instances. Accordingly, modest enhancement of N O levels should afford cardioprotection during reperfusion.