20-Hydroxyeicosatetraenoic acid is an endogenous vasoconstrictor of canine renal arcuate arteries

Yunn Hwa Ma, Debebe Gebremedhin, Michal L. Schwartzman, J R Falck, Joan E. Clark, Bettie Sue Masters, David R. Harder, Richard J. Roman

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

Abstract

Recent studies have indicated that renal arteries can produce 20- hydroxyeicosatetraenoic acid (20-HETE) and suggest the potential involvement of a P450 metabolite of arachidonic acid in the myogenic activation of canine renal arteries. In the present study, the effects of 20-HETE on isolated canine renal arcuate arteries were studied. Administration of 20-HETE to the bath or the lumen at concentrations of 0.01-1 μM produced a graded reduction in the diameter of these vessels. In contrast, 19(R)-HETE was a vasodilator, whereas 19(S)-HETE was relatively inactive. The vasoconstrictor response to 20-HETE was not altered by the cyclooxygenase inhibitor indomethacin, endoperoxide/thromboxane receptor antagonist SQ29548, or combined blockade of the cyclooxygenase, lipoxygenase, and P450 pathways using indomethacin, baicalein, and 7-ethoxyresorufin. The response to 20-HETE was associated with depolarization and a sustained increase in the intracellular calcium concentration in renal vascular smooth muscle cells. Patch-clamp studies indicated that 20-HETE significantly reduced mean open time, the open-state probability, and the frequency of opening of a 117-pS K+ channel recorded from renal vascular smooth muscle cells in the cell-attached mode. Microsomes prepared from the renal cortex of dogs produced 20-HETE and 20- carboxyarachidonic acid when incubated with [14C]arachidonic acid. These results indicate that 20-HETE is an endogenous constrictor of canine renal arcuate arteries. The vasoconstrictor response to 20-HETE resembles the myogenic activation of these vessels after elevations in transmural pressure and suggests a potential role for this substance in the regulation of renal vascular tone.

Original languageEnglish (US)
Pages (from-to)126-136
Number of pages11
JournalCirculation research
Volume72
Issue number1
DOIs
StatePublished - 1993

Keywords

  • 20-hydroxyeicosatetraenoic acid
  • cytochrome P450
  • intracellular calcium
  • kidney
  • myogenic response
  • potassium channels
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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