Relative contributions of cyclooxygenase- and cytochrome p450 omega-hydroxylase-dependent pathways to hypoxic dilation of skeletal muscle resistance arteries

This study determined the contribution of prostanoids, cytochrome P450 (CP4 50) 4A enzyme metabolites of arachidonic acid, and other potential mediator s of hypoxic dilation of isolated rat skeletal muscle resistance arteries. Gracilis arteries (GA) were viewed via television microscopy and dilator re sponses to hypoxia (reduction in superfusate and perfusate PO2 from similar to 145 to similar to 40 mm Hg) were measured with a video micrometer. Hypo xic dilation of gracilis arteries was severely impaired by either endotheli um removal or cyclooxygenase inhibition with indomethacin, but not by nitri c oxide synthase inhibition with L-NAME. Treatment of GA with 17-octadecyno ic acid (17-ODYA) alone to inhibit CP450 4A enzymes significantly reduced h ypoxic dilation from control levels. Treatment of vessels with N-methylsulf onyl-6-(2-proparglyoxyphenyl)hexanoic acid (MS-PPOH) to inhibit the product ion of epoxyeicosatrienoic acids (EETs) did not alter hypoxic dilation, alt hough treatment with dibromododecenyl-methylsulfimide (DDMS) to inhibit 20- hydroxyeicosatetraenoic acid (20-HETE) production had similar effects as 17 -ODYA. Treatment of GA with 6(Z),15(Z)-20-HEDE, a competitive antagonist of the actions of 20-HETE, mimicked the effects of 17-ODYA and DDMS treatment on hypoxic dilation. These results suggest that hypoxic dilation of skelet al muscle resistance arteries primarily represents the effects of enhanced prostanoid release from vascular endothelium, although a contribution of re duced 20-HETE production via CP450 omega -hydroxylase enzymes also regulate s hypoxic dilation of these vessels. Copyright (C) 2001 S.Karger AG, Basel.