Abstract
Objective: 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 transrnural pressure.
Original language | English (US) |
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Pages (from-to) | 45-55 |
Number of pages | 11 |
Journal | Microcirculation |
Volume | 8 |
Issue number | 1 |
DOIs | |
State | Published - 2001 |
Keywords
- 17-ODYA
- 20-HETE
- Cytochrome P450 4A enzymes
- Cytochrome P450 ω-hydroxylase
- DDMS
- K channels
- Myogenic response
- Vascular smooth muscle
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)