Relative contributions of cyclooxygenase- and cytochrome P450 ω-hydroxylase-dependent pathways to hypoxic dilation of skeletal muscle resistance arteries

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

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27 Scopus citations

Abstract

This study determined the contribution of prostanoids, cytochrome P450 (CP450) 4A enzyme metabolites of arachidonic acid, and other potential mediators of hypoxic dilation of isolated rat skeletal muscle resistance arteries. Gracilis arteries (GA) were viewed via television microscopy and dilator responses to hypoxia (reduction in superfusate and perfusate PO2 from ∼145 to ∼40 mm Hg) were measured with a video micrometer. Hypoxic dilation of gracilis arteries was severely impaired by either endothelium removal or cyclooxygenase inhibition with indomethacin, but not by nitric oxide synthase inhibition with L-NAME. Treatment of GA with 17-octadecynoic acid (17-ODYA) alone to inhibit CP450 4A enzymes significantly reduced hypoxic dilation from control levels. Treatment of vessels with N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (MS-PPOH) to inhibit the production of epoxyeicosatrienoic acids (EETs) did not alter hypoxic dilation, although treatment with dibromo-dodecenyl-methylsulfimide (DDMS) to inhibit 20-hydroxyeicosatetraenoic acid (20-HETE) production had similar effects as 17-ODYA. Treatment of GA with 6(Z),15(Z)-20-HEDE, a competitive antagonist of the actions of 20-HETE, mimicked the effects of 17-ODYA and DDMS treatment on hypoxic dilation. These results suggest that hypoxic dilation of skeletal muscle resistance arteries primarily represents the effects of enhanced prostanoid release from vascular endothelium, although a contribution of reduced 20-HETE production via CP450 ω-hydroxylase enzymes also regulates hypoxic dilation of these vessels.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalJournal of Vascular Research
Volume38
Issue number4
DOIs
StatePublished - Aug 6 2001

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Keywords

  • 20-HETE
  • 20-Hydroxyeicosatetraenoic acid
  • Arachidonic acid metabolism
  • Cytochrome P450 4A enzymes
  • Epoxyeicosatrienoic acid
  • Hypoxia
  • K channels
  • K channels
  • Microcirculation
  • Oxygen
  • Potassium channels
  • Vascular reactivity
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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