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 atherosclerosis. 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 turn, stimulates endothelial NO synthase activation, NO release and prolongation of vasodilation. Reactive hyperemia, myogenic vasodilation and vasodilator effects of acetylcholine and bradykinin are all mediated by NO. Ischemic preconditioning, which protects the myocardium from cellular damage and arrhythmias, is itself linked with NO and 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 pressure and so it is likely that NO is an important blood flow regulatory mechanism in exercise. This phenomenon may account for the beneficial effects of exercise seen in atherosclerotic individuals. Whilst NO plays a protective role in preventing atherosclerosis via superoxide anion scavenging, risk factors such as hypercholesterolemia reduce NO release leading the way for endothelial dysfunction and atherosclerotic lesions. Exercise reverses this process by stimulating NO synthesis and release. Other factors impacting on the activity of NO include estrogens, endothelins, adrenomedullin and adenosine, the last appearing to be a compensatory pathway for coronary control in the presence of NO inhibition. These studies reinforce the pivotal role played by the substance in the control of coronary circulation.
Gattullo
D
D
Dipartimento di Scienze Cliniche e Biologische, Università di Torino, Ospedale S. Luigi, Orbassano, Italy.
Pagliaro
P
P
Marsh
N A
NA
Losano
G
G
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*
D009569:Nitric Oxide