title: Transduction of physical force by the vascular wall Role of phospholipase C and cytochrome P450 metabolites of arachidonic acid.
abstract: The blood vessel wall responds actively to an elevation in transmural pressure. This pressure-induced myogenic response is thought to set the basal level of vascular tone upon which metabolic and neural influences operate in concert to regulate organ blood flow. The cellular mechanisms that mediate the vascular muscle response to mechanical deformation via a changing transmural pressure include membrane depolarization, activation of phospholipase C, and a rise in intracellular [Ca(2+)](i), which appear to be nonadapting-remaining active as long as the pressure stimulus is applied. This brief review addresses some of the cellular events mediating transduction of transmural pressure by the vessel wall. Two possible mechanisms that are responsible for the nonadapting nature of pressure-induced myogenic tone are also explored, namely, formation of a P450 metabolite of arachidonic acid, which acts to buffer activation of K(+) channels as intracellular Ca(2+) rises, and direct activation of Ca(2+) channels by diacylglycerol. Evidence is provided suggesting that activation of phospholipase C is responsible for both the release of the arachidonic acid substrate for P450 enzymes and for the formation of diacylglycerol via its action on membrane-bound phospholipids.
authors.affiliation: David R. Harder, Jayashree Narayanan, Debebe Gebremedhin, and Richard J. Roman are at the Cardiovascular Research Center Medical College of Wisconsin, Milwaukee, WI 53226, USA; the Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Harder
authors.forename: J
authors.initials: J
authors.lastname: Narayanan
authors.forename: D
authors.initials: D
authors.lastname: Gebremedhin
authors.forename: R J
authors.initials: RJ
authors.lastname: Roman