Endothelium Dependent Regulation of Vascular Tone

The endothelium is an inner layer of the vascular wall which can produce vasoactive medi­ators alone or in response to various types of stimuli. Endothelium derived vasoactive substances can cause either endothelium dependent vasoconstriction or vasodilatation, and they play a significant role in intrinsic vascular tone regulation. By acting on different pathways of intra­cellular signaling, endothelin-1 and some arachidonic acid metabolites lead to an increased calcium concentration in vascular smooth muscles that finally leads to constriction. Endothelium dependent vasorelaxants include nitric oxide, carbon monoxide, prostacyclin, endothelium derived hyperpolarizing factor and endocannabinoids. In addition, studies have recently revealed that the vascular endothelium is responsible for the synthesis of a novel cyclic peptide termed urotensin-II, which exhibits vasoactive properties. Urotensin-II was orig­inally isolated from the fish neurosecretor organ, but later on various isoforms of this peptide have also been identified in other animal species and in humans. Urotensin-II and its G-pro- tein coupled receptor are widely represented in different tissues, including the vascular wall.