New insights into nitric oxide and coronary circulation

Since its discovery over 20 years ago as an intercellular messenger, nitric oxide (NO), has been extensively studied with regard to its involvement in the control of the circulation and, more recently, in the prevention of at herosclerosis. The importance of NO in coronary blood flow control has also been recognized. NO-independent vasodilation causes increased shear stress within the blood vessel which, in rum, stimulates endothelial NO synthase activation, NO release and prolongation of vasodilation. Reactive hyperemia , myogenic vasodilation and vasodilator effects of acetylcholine and bradyk inin are all mediated by NO. Ischemic preconditioning, which protects the m yocardium from cellular damage and arrhythmias, is itself linked with NO an d both the first and second windows of protection may be due to NO release. Exercise increases NO synthesis via increases in shear stress and pulse pr essure and so it is likely that NO is an important blood flow regulatory me chanism in exercise. This phenomenon may account for the beneficial effects of exercise seen in atherosclerotic individuals. Whilst NO plays a protect ive role in preventing atherosclerosis via superoxide anion scavenging, ris k factors such as hypercholesterolemia reduce NO release leading the way fo r endothelial dysfunction and atherosclerotic lesions. Exercise reverses th is process by stimulating NO synthesis and release. Other factors impacting on the activity of NO include estrogens, endothelins, adrenomedullin and a denosine, the last appearing to be a compensatory pathway for coronary cont rol in the presence of NO inhibition. These studies reinforce the pivotal r ole played by the substance in the control of coronary circulation.