Local regulation of the coronary circulation in health and disease: role of nitric oxide and endothelin

Coronary artery disease is the leading cause of morbidity and mortality in western countries. Its pathogenesis is unknown, but involves enhanced vasoconstriction, increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration and extracellular matrix formation of vascular smooth muscle. The endothelium lies in a strategic anatomical position between circulating blood and vascular smooth muscle cells. This supports the concept that dysfunction of these cells significantly contributes to coronary artery disease. Besides other mediators, endothelial cells are a source of nitric oxide and endothelin. Nitric oxide is a vasodilator, an inhibitor of both platelet function and proliferation and migration of vascular smooth muscle. Endothelin is a potent vasoconstrictor that facilitates proliferation. Under pathological conditions, in particular the presence of cardiovascular risk factors, endothelial dysfunction occurs and is a major contributor to the increase in platelet vessel wall interaction, vasoconstriction and proliferation in the coronary system. Endothelium-dependent vasodilation is usually reduced and endothelium-dependent constrictor responses, as well as endothelin production, are augmented. Hence, endothelial cells are important targets and mediators of coronary artery disease