Abstract
The present study determined the role of 20-hydroxyeicosatetraenoic acid [20-HETE; produced by ω-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 Ca2+-activated potassium (KCa) 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 KCa channels through a receptor-mediated process.
Original language | English (US) |
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Pages (from-to) | H1066-H1074 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 280 |
Issue number | 3 49-3 |
DOIs | |
State | Published - 2001 |
Keywords
- 17-octadecynoic acid
- Cytochrome P-450 4A enzymes
- Cytochrome P-450 ω-hydroxylase
- Dibromododecynyl-methylsulfimide
- Potassium channels
- Vascular smooth muscle
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)