Endogenous Events Modulating Myogenic Regulation of Cerebrovascular Function.

Endogenous Events Modulating Myogenic Regulation of Cerebrovascular Function. Curr Vasc Pharmacol. 2013 Sep 25; Authors: Gebremedhin D, Gopalakrishnan S, Harder DR Abstract The existence of arterial myogenic tone was first described by Bayliss in 1902, however, its association with pressure-dependent membrane depolarization was not observed until 1984. The factors that mediate myogenic arterial constriction remain unknown. One possible clue was a finding by our laboratory that cerebral arterial muscle cells express CYP 4A ω-hydroxylase enzymes that catalyzes the formation of the potent vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid (AA), the production of which increased by elevations of intravascular pressure. 20-HETE activates protein kinase C (PKC), inhibits Ca2+-activated K+ (KCa) channels, depolarizes arterial muscle cell membrane, activates L-type Ca2+ channels, increase intracellular Ca2+ ([Ca2+]i) and mediates autoregulation of cerebral blood flow. Emerging evidence indicates that 20-HETE levels increase in ischemia/reperfusion injury and stimulates production of reactive oxygen species (ROS) resulting in oxidative stress induced ischemic stroke injury, which can be prevented by inhibition of 20-HETE synthesis or action. The brain also expresses CYP epoxygenases that convert AA to the vasodilator epoxyeicosatrienoic acids (EETs), the production of which increases in ischemia and provide protection agai...
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research