20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague-Dawley rats.
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.
Frisbee
J C
JC
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA. jfrisbee@mcw.edu
Roman
R J
RJ
Falck
J R
JR
Krishna
U M
UM
Lombard
J H
JH
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D042926:Cytochrome P-450 CYP4A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply*; D026902:Potassium Channel Blockers; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology
D000577:Amides; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D026902:Potassium Channel Blockers; D013450:Sulfones; C047008:17-octadecynoic acid; 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