Faculty Collaboration Database

Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries. Microvasc Res 2001 Nov;62(3):271-83

Date

10/27/2001

Pubmed ID

11678630

DOI

10.1006/mvre.2001.2341

Scopus ID

2-s2.0-0034756380 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

This study determined the contribution of cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid in mediating the constriction of isolated rat skeletal muscle resistance arteries in response to elevated PO2. Gracilis arteries (GA) were viewed via television microscopy and constrictor responses to elevated PO2 were measured with a video micrometer. Endothelium removal and treatment of GA with 17-octadecynoic acid (17-ODYA; suicide substrate inhibitor of CP450 4A enzymes) impaired oxygen-induced constriction of the vessels; treatment of endothelium-denuded GA with 17-ODYA eliminated responses to elevated PO2. NOS inhibition and inhibition of EET production had no effect on oxygen-induced constriction of the vessels, although cyclooxygenase inhibition with indomethacin impaired GA responses to elevated PO2. Treatment of GA with dibromododecenyl methylsulfimide (DDMS; inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) production) or 6(Z),15(Z)-20-HEDE (antagonist for 20-HETE receptors) mimicked the effects of 17-ODYA on GA responses to elevated PO2. Treatment of vessels with iberiotoxin or glibenclamide reduced the constriction of the vessels in response to elevated PO2 while treatment with both K+ channel blockers eliminated oxygen-induced constriction of the vessels. Following treatment of GA with indomethacin and 20-HETE, the vessels failed to respond to elevated PO2. These results suggest that oxygen-induced constriction of skeletal muscle resistance arteries represents the combined effects of reduced prostanoid release from the vascular endothelium and enhanced 20-HETE production in vascular smooth muscle cells.

Author List

Frisbee JC, Krishna UM, Falck JR, Lombard JH

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

Animals
Arachidonic Acid
Arteries
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Endothelium, Vascular
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Male
Microscopy, Video
Muscle, Skeletal
Muscle, Smooth
Oxygen
Partial Pressure
Potassium Channel Blockers
Prostaglandins
Rats
Rats, Sprague-Dawley
Vascular Resistance
Vasoconstriction