TRANSDUCTION OF PHYSICAL FORCE BY THE VASCULAR WALL - ROLE OF PHOSPHOLIPASE-C AND CYTOCHROME-P450 METABOLITES OF ARACHIDONIC-ACID

The blood vessel wall responds actively to an elevation in transmural pressure. This pressure-induced myogenic response is thought to set th e basal level of vascular tone upon which metabolic and neural influen ces operate in concert to regulate organ blood flow. The cellular mech anisms that mediate the vascular muscle response to mechanical deforma tion via a changing transmural pressure include membrane depolarizatio n, activation of phospholipase C, and a rise in intracellular [Ca2+](i ), which appear to be nonadapting-remaining active as long as the pres sure stimulus is applied. This brief review addresses some of the cell ular events mediating transduction of transmural pressure by the vesse l wall. Two possible mechanisms that are responsible for the nonadapti ng nature of pressure-induced myogenic tone are also explored namely, formation of a P450 metabolite of arachidonic acid, which acts to buff er activation of K+ channels as intracellular Ca2+ rises, and direct a ctivation of Ca2+ channels by diacylglycerol. Evidence is provided sug gesting that activation of phospholipase C is responsible for both the release of the arachidonic acid substrate for P450 enzymes and for th e formation of diacylglycerol via ifs action on membrane-bound phospho lipids.