20-HETE modulates myogenic response of skeletal muscle resistance arteries from hypertensive Dahl-SS rats

Jefferson C. Frisbee, Richard J. Roman, U. Murali Krishna, J R Falck, Julian H. Lombard

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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 languageEnglish (US)
Pages (from-to)H1066-H1074
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number3 49-3
DOIs
StatePublished - 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)

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