20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague-Dawley rats

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

Research output: Contribution to journalArticle

30 Scopus citations

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 languageEnglish (US)
Pages (from-to)45-55
Number of pages11
JournalMicrocirculation
Volume8
Issue number1
DOIs
StatePublished - Dec 1 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)

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