In vivo location and mechanism of EDHF-mediated vasodilation in canine coronary microcirculation

Yasuhiro Nishikawa, David W Stepp, William M. Chilian

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Responses of epicardial coronary arterioles to ACh were measured using stroboscopic fluorescence microangiography in dogs (n = 38). ACh (0.1 and 0.5 μg · kg-1 · min-1 ic) dilated small (<100 μm, 11 ± 2 and 19 ± 2%, respectively) and large (>100 μm, 6 ± 3 and 13 ± 3%, respectively) arterioles at baseline. Combined administration of N(ω)-monomethyl-L- arginine (L-NMMA; 1.0 μmol/min ic) and indomethacin (10 mg/kg iv) eliminated ACh-induced dilation in large coronary arterioles but only partially attenuated that in small arterioles. Suffusion of a buffer containing 60 mM KCl (high KCl) completely abolished cromakalim-induced dilation in arterioles and in combination with L-NMMA plus indomethacin completely blocked ACh- induced dilation in small arterioles. This indicated that the vasodilation to ACh that persists in small arterioles after administration of L-NMMA and indomethacin is mediated via a hyperpolarizing factor. The ACh-induced vasodilation remaining after L-NMMA and indomethacin was completely blocked by the large-conductance potassium-channel antagonist iberiotoxin or by epicardial suffusion of miconazole or metyrapone, inhibitors of cytochrome P- 450 enzymes. These observations are consistent with the view that endothelium-derived hyperpolarizing factor (EDHF) is a product of cytochrome P-450 enzymes and produces vasodilation by the opening of large-conductance potassium channels. We conclude that ACh-induced dilation in large coronary arterioles is mediated mainly by nitric oxide (NO), whereas, in small arterioles both NO and EDHF mediate dilation to ACh. These data provide the first direct evidence for an in vivo role of EDHF in small coronary arterioles.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume277
Issue number3 46-3
StatePublished - Sep 1 1999
Externally publishedYes

Keywords

  • Coronary circulation
  • Endothelium-dependent dilation
  • Endothelium-derived hyperpolarizing factor
  • Hyperpolarization

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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