Endothelium-derived relaxing and contracting factors.

Abstract

Since the description of the essential role of the endothelium in mediating relaxations due to acetylcholine in mammalian arteries, it has become obvious that endothelial cells release several relaxing and contracting 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. There is strong evidence that the major endothelium-derived relaxing factor (EDRF) is the free radical nitric oxide (NO) formed enzymatically from L-arginine. Endothelium-dependent relaxations caused by EDRF are induced through increases in the activity of soluble guanylate cyclase in the smooth muscle. Other relaxing factors, such as prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) contribute to endothelium-dependent relaxations. Beside the recently described and chemically identified peptide endothelin, at least two other endothelium-derived contracting factors appear to exist. The mechanisms by which endothelium-derived contracting factors activate vascular smooth muscle are not yet clear. In certain clinical situations an impairment of the production of EDRF in face of a maintained or augmented release of contracting factors may contribute to the occurrence of localized vasospasm or generalized increases in peripheral resistance.