Endothelium-derived relaxing factors

Abstract

The endothelium plays an essential role in mediating relaxations of vascular smooth muscle in response to acetylcholine and other vasodilators. Indeed, endothelial cells can release several relaxing substances. The release is activated by a variety of agents including circulating hormones, autacoids, and products liberated by aggregating platelets, but also by changes in shear stress exerted by the blood. The major endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) formed enzymatically from L-arginine by the constitutive NO-synthase of the endothelial cells. Endothelium-dependent relaxations caused by EDRF are accompanied by increases in the activity of the soluble guanylate cyclase of the vascular smooth muscle cells. Other relaxing factors, such as prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) contribute to endothelium-dependent relaxations. In certain clinical situations an impairment of the production of EDRF (and EDHF?) may contribute to the occurrence of localized vasospasm or generalized increases in peripheral resistance, and set in motion the atherosclerotic process.