Role of prostanoids and 20-HETE in mediating oxygen-induced constriction of skeletal muscle resistance arteries.
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.
Frisbee
J C
JC
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Krishna
U M
UM
Falck
J R
JR
Lombard
J H
JH
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001158:Arteries / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D026902:Potassium Channel Blockers; D011453:Prostaglandins; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D010100:Oxygen