The vascular endothelium and nitric oxide

Abstract

The endothelium is a single layer of cells lining blood and lymphatic vessels. The endothelium separates the contents of the lumen of blood vessels from the underlying connective tissue and vascular smooth muscle. It therefore serves as a semi-permeable barrier, regulating the movement of substances from the lumen of the blood vessel to the interstitium, and vice-versa. The endothelium also acts as a transducer of signals from the lumen to the vascular smooth muscle, and plays a crucial role in regulating inflammatory responses and regulating the growth of new blood vessels. Nitric oxide (NO) is produced via the metabolism of L-arginine by a family of enzymes known as nitric oxide synthases (NOS). Endothelial NO production occurs primarily via the appropriately named endothelial NOS (eNOS). In recent years a great deal has been learned about the molecular regulation of eNOS activity. Moreover, the availability of selective NOS inhibitors and of genetically modified mice that lack eNOS has aided in gaining a better understanding of the physiological and pathophysiological roles of eNOS. NO is an important regulator of blood pressure and of local tissue blood flow. Along with prostacyclin, endothelial NO production is crucial to the regulation of platelet aggregation, as well as in regulating leukocyte adherence to endothelium (thus modulating inflammatory responses). In situation of endothelial dysfunction the impairment og No synthesis contributes to elevated blood pressure, enhanced inflammatory reactions, impaired tissue blood flow and thrombogenesis. Controlled delivery of NO from exogenoues sources may represent an attractive approach to the treatment of disorders characterized by endothelial dusfunction.