20‐HETE Contributes to Myogenic Activation of Skeletal Muscle Resistance Arteries in Brown Norway and Sprague‐Dawley Rats

Abstract

ABSTRACTObjective: To evaluate the role of 20‐hydroxyeicosatetraenoic acid (20‐HETE), a product of arachidonic acid ω‐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.