Nitric oxide signalling in the regulation of cardiovascular and platelet function

Nitric oxide (NO) exerts important protective actions on the cardiovascular system. Generated from L-arginine by the action of endothelial (or type 3) nitric oxide synthase (NOS3), NO regulates vascular tone in humans and causes endothelium-dependent vasodilation. Additionally endothelium-derived NO exerts antioxidant, antiproliferative and anti-inflammatory properties, thus playing an important role in inhibiting the atherosclerotic process. With regard to effects on platelet function, NO produced by both endothelial cells and platelets has important antithrombotic effects by decreasing platelet activation, a phenomenon which contributes importantly to the thrombotic tendency which accompanies a variety of cardiovascular disease states. Additionally, by inhibiting platelet activation, NO prevents heterotypic aggregation between platelets and monocytes, thereby reducing monocyte-platelet aggregates in the circulation which are believed to play an important pathophysiological role in the initiation and progression of atherosclerosis. New therapeutic interventions aimed at improving NO availability have been investigated in animal as well as in vitro studies and show considerable promise, but it remains to be seen whether such therapies will be equally efficacious in humans clinically.