Faculty Collaboration Database

Relative contributions of cyclooxygenase- and cytochrome P450 omega-hydroxylase-dependent pathways to hypoxic dilation of skeletal muscle resistance arteries. J Vasc Res 2001;38(4):305-14

Date

07/17/2001

Pubmed ID

11455201

DOI

10.1159/000051061

Scopus ID

2-s2.0-0034921573 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

This study determined the contribution of prostanoids, cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid, and other potential mediators of hypoxic dilation of isolated rat skeletal muscle resistance arteries. Gracilis arteries (GA) were viewed via television microscopy and dilator responses to hypoxia (reduction in superfusate and perfusate PO2 from approximately 145 to approximately 40 mm Hg) were measured with a video micrometer. Hypoxic dilation of gracilis arteries was severely impaired by either endothelium removal or cyclooxygenase inhibition with indomethacin, but not by nitric oxide synthase inhibition with L-NAME. Treatment of GA with 17-octadecynoic acid (17-ODYA) alone to inhibit CP450 4A enzymes significantly reduced hypoxic dilation from control levels. Treatment of vessels with N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (MS-PPOH) to inhibit the production of epoxyeicosatrienoic acids (EETs) did not alter hypoxic dilation, although treatment with dibromo-dodecenyl-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 skeletal muscle resistance arteries primarily represents the effects of enhanced prostanoid release from vascular endothelium, although a contribution of reduced 20-HETE production via CP450 omega-hydroxylase enzymes also regulates hypoxic dilation of these vessels.

Author List

Frisbee JC, Roman RJ, Krishna UM, Falck JR, Lombard JH

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acid
Arteries
Cyclooxygenase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Endothelium, Vascular
Enzyme Inhibitors
Fatty Acids, Unsaturated
Hydroxyeicosatetraenoic Acids
Hypoxia
Indomethacin
Male
Mixed Function Oxygenases
Muscle, Skeletal
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Oxygen
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Vascular Resistance
Vasodilation