Endothelium-derived hyperpolarizing factor in coronary microcirculation: Responses to arachidonic acid

C. L. Oltman, N. L. Kane, J. L. Fudge, N. L. Weintraub, K. C. Dellsperger

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

In coronary resistance vessels, endothelium-derived hyperpolarizing factor (EDHF) plays an important role in endothelium-dependent vasodilation. EDHF has been proposed to be formed through cytochrome P-450 monooxygenase metabolism of arachidonic acid (AA). Our hypothesis was that AA-induced coronary microvascular dilation is mediated in part through a cytochrome P-450 pathway. The canine coronary microcirculation was studied in vivo (beating heart preparation) and in vitro (isolated microvessels). Nitric oxide synthase (NOS) (Nω-nitro-L-arginine, 100 μM) and cyclooxygenase (indomethacin, 10 μM) or cytochrome P-450 (clotrimazole, 2 μM) inhibition did not alter AA-induced dilation. However, when a Ca2+-activated K+ channel channel or cytochrome P-450 antagonist was used in combination with NOS and cyclooxygenase inhibitors, AA-induced dilation was attenuated. We also show a negative feedback by NO on NOS-cyclooxygenase-resistant AA-induced dilation. We conclude that AA-induced dilation is attenuated by cytochrome P-450 inhibitors, but only when combined with inhibitors of cyclooxygenase and NOS. Therefore, redundant pathways appear to mediate the AA response in the canine coronary microcirculation.

Original languageEnglish (US)
Pages (from-to)H1553-H1560
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number4 50-4
DOIs
StatePublished - 2001

Keywords

  • Coronary circulation
  • Coronary microcirculation
  • Intravital microscopy

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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