Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle

D. Gebremedhin, Y. H. Ma, J R Falck, R. J. Roman, M. VanRollins, D. R. Harder

Research output: Contribution to journalArticle

269 Scopus citations

Abstract

Microsomal preparations of cat brain incubated with [14C]arachidonic acid produced epoxyeicosatrienoic acids (EETs) that eluted with the same retention times as synthetically prepared 5,6-, 8,9-, and 11,12-EETs. These compounds dilated serotonin-preconstricted, pressurized cat cerebral arteries in a dose-dependent fashion. Epoxide formation was not found in mitochondrial fractions and was dependent on the presence of NADPH. The maximum effects of 8,9-EET and 11,12-EET were greater than those of 5,6-EET. The cellular basis of this vasodilation was further investigated by examining the effects of 8,9-EET and 11,12-EET on K+ channel activity in vascular muscle cells freshly isolated from cat cerebral arteries. Both 8,9-EET and 11,12-EET increased the frequency of opening, mean open time, and open-state probability of a 98-pS K+ channel recorded in the cell-attached mode with 145 mM KCl in the pipette and 4.7 mM KCl in the bath. Blockade of K+ channel activity with tetraethylammonium attenuated the vasodilatory effects of 11,12-EET on serotonin-preconstricted cat cerebral arteries. These results suggest that endogenously formed EETs may participate in local regulation of cerebral blood flow by dilating cerebral arteries through a mechanism that involves activation of K+ channels.

Original languageEnglish (US)
Pages (from-to)H519-H525
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume263
Issue number2 32-2
DOIs
StatePublished - 1992

Keywords

  • cerebral circulation
  • cytochrome P
  • epoxygenase
  • high-performance liquid chromatography
  • patch clamp
  • single potassium channels

ASJC Scopus subject areas

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

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