Faculty Collaboration Database

20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague-Dawley rats. Microcirculation 2001 Feb;8(1):45-55

Date

04/12/2001

Pubmed ID

11296852

Scopus ID

2-s2.0-0035258437 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

OBJECTIVE: To evaluate the role of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of arachidonic acid omega-hydroxylation via cytochrome P450 (CP450) 4A enzymes, in regulating myogenic activation of skeletal muscle resistance arteries from normotensive Brown Norway (BN) and Sprague-Dawley (SD) rats.

METHODS: Gracilis arteries (GA) were isolated from each animal, viewed via television microscopy, and vessel diameter responses to elevated transmural pressure were measured with a video micrometer under control conditions and following pharmacological inhibition of the CP450 4A enzyme system.

RESULTS: Under control conditions, GA from both rat groups exhibited strong, endothelium-independent myogenic activation, which was impaired following treatment with either 17-octadecynoic acid (17-ODYA) or dibromo-dodecenylmethylsulfimide (DDMS), two mechanistically different inhibitors of 20-HETE production. The addition of tetraethylammonium (KCa channel inhibitor) to 17-ODYA-treated GA restored myogenic reactivity to levels comparable to those under control conditions. Treatment of GA from BN and SD rats with 6(Z),15(Z)-20-HEDE, a selective antagonist for 20-HETE receptors, mimicked the effects of 17-ODYA and DDMS treatment on myogenic reactivity.

CONCLUSIONS: These results suggest that the production of 20-HETE via CP450 4A enzymes contributes to the myogenic activation of skeletal muscle resistance arteries from normotensive BN and SD rats. 20-HETE may act through a receptor-mediated process to block vascular smooth muscle KCa channels in response to the elevated transmural pressure.

Author List

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

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

Amides
Animals
Arteries
Cytochrome P-450 CYP4A
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Endothelium, Vascular
Enzyme Inhibitors
Fatty Acids, Unsaturated
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Male
Mixed Function Oxygenases
Muscle, Skeletal
Potassium Channel Blockers
Rats
Rats, Inbred BN
Rats, Sprague-Dawley
Sulfones
Vascular Resistance