Working under pressure: coronary arteries and the endothelin system.

Endogenous endothelin-1-dependent (ET-1) tone in coronary arteries depends on the balance between ET(A) and ET(B) receptor-mediated effects and on parameters such as receptor distribution and endothelial integrity. Numerous studies highlight the striking functional interactions that exist between nitric oxide (NO) and ET-1 in the regulation of vascular tone. Many of the cardiovascular complications associated with cardiovascular risk factors and aging are initially attributable, at least in part, to endothelial dysfunction characterized by a dysregulation between NO and ET-1. The contribution of the imbalance between smooth muscle ET(A/B) and endothelial ET(B) receptors to this process is poorly understood. An increased contribution of ET-1 that is associated with a proportional decrease in that of NO accompanies the development of coronary endothelial dysfunction, coronary vasospasm, and atherosclerosis. These data form the basis for the rationale of testing therapeutic approaches counteracting ET-1-induced cardiovascular dysfunction. It remains to be determined whether the beneficial role of endothelial ET(B) receptors declines with age and risk factors for cardiovascular diseases, revealing smooth muscle ET(B) receptors with proconstricting and proinflammatory activities.