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-hydroxyeicosatraenoic acid (20-WETE), a product of arachidonic acid omega -hydroxylation via cytochrome P450 (CP 450) 4A enzymes, in regulating myogenic activation of skeletal muscle resis tance arteries from normotensive Brown Norway (BN) and Sprague-Dawley (SD) rats. Methods: Gracilis arteries (GA) mere isolated from each animal, viewed via television microscopy, and vessel diameter responses to elevated transmural pressure. We 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-ocradecynoic acid (17-ODYA) or dibromo-dodecenyl- methylsulfimide (DDMS), two mechanistically different inhibitors of 20-HETE production. The addition of tetraethylammonium (K-Ca channel inhibitor) to 17-ODYA-treated GA restored myogenic reactivity to levels comparable to th ose under control conditions. Treatment of GA from BN and SD rats with 6(Z) ,15(Z)-20-HEDE; a selective antagonist fur 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 resis tance arteries from normotensive BN and SD rats. 20-HETE may act through a re receptor-mediated process to block vascular smooth muscle K-Ca channels in response to the elevated transmural pressure.