Endothelium-dependent vascular responses. Mediators and mechanisms.

The nonthrombogenic and high solute and water permeability properties of the vascular endothelium have long been recog- nized as essential components of normal microvascular integ- rity. In addition to the more recent recognition of other hemo- static as well as proproliferative and cytoadhesive properties, the past decade has witnessed a growing awareness that this endothelial monolayer is also capable of intrinsic modulation of vascular tone by elaborating several potent vasoactive sub- stances. Two impressive vasorelaxants are prostacyclin and endothelium-derived relaxation factor (EDRF),' the latter at least in part composed of nitric oxide (NO). In addition, vascu- lar endothelium has been shown recently to synthesize a novel polypeptide, termed endothelin, which exhibits potent vaso- constrictor properties. Prostacyclin, a major metabolite of the cyclooxygenase pathway in vessel walls and the subject of in- tense study for more than a decade, has recently been reviewed (1). Due to space constraints, this brief review2 will therefore focus on other recently described endothelium-dependent va- soactive mediators, particularly NO and endothelin.