20-HETE modulates myogenic response of skeletal muscle resistance arteries from hypertensive Dahl-SS rats.
The present study determined the role of 20-hydroxyeicosatetraenoic acid [20-HETE; produced by omega-hydroxylation of arachidonic acid via cytochrome P-450 (CP450) 4A enzymes] in regulating myogenic activation of skeletal muscle resistance arteries from normotensive (NT) and hypertensive (HT) Dahl salt-sensitive (SS) rats. Gracilis arteries (GA) were isolated from each rat and viewed via television microscopy, and changes in vessel diameter with altered transmural pressure were measured with a video micrometer. Under control conditions, GA from both groups exhibited strong, endothelium-independent myogenic activation. Treatment of GA with 17-octadecynoic acid (17-ODYA; inhibitor of CP450 4A enzymes) did not alter myogenic activation in NT rats, but impaired this response in HT animals. Treatment of GA from HT rats with dibromo-dodecynyl-methylsulfimide (DDMS; inhibitor of 20-HETE production) impaired myogenic activation, as did application of 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, an antagonist for 20-HETE receptors. Application of iberiotoxin, a Ca(2+)-activated potassium (K(Ca)) channel inhibitor, restored myogenic activation from HT rats treated with DDMS. These results suggest that myogenic activation of skeletal muscle resistance arteries from NT Dahl-SS rats does not depend on CP450, whereas myogenic activation of these vessels in HT Dahl-SS rats is partly a function of 20-HETE production, inhibiting K(Ca) channels through a receptor-mediated process.
Frisbee
J C
JC
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Roman
R J
RJ
Krishna
U M
UM
Falck
J R
JR
Lombard
J H
JH
D000577:Amides / Q000494:pharmacology; D000818:Animals; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D013450:Sulfones / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000577:Amides; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015221:Potassium Channels; D013450:Sulfones; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; C117975:DDMS; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; C409986:cytochrome P-450 omega-hydroxylase