Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles

John D. Imig, Ai Ping Zou, Dave E. Stec, David R. Harder, J R Falck, Richard J. Roman

Research output: Contribution to journalArticlepeer-review

251 Scopus citations

Abstract

The present study examined whether preglomerular arterioles of the rat produce 20-hydroxyeicosatetraenoic acid (20-HETE) and whether 20-HETE is vasoactive on these vessels. Rat preglomerular arterioles produced 20-HETE (4.8 ± 1.0 pmol · min-1 · mg-1, n = 7) and, to a lesser extent, 14-, 15-, 11-, and 12-dihydroxyeicosatetraenoic acid, 6-ketoprostaglandin F(1α), and prostaglandin E2 when incubated with [14C] arachidonic acid. The results of immunoblotting and reverse-transcription polymerase chain reaction experiments indicate that these vessels express mRNA and protein for a P-450 4A2 enzyme. With the use of a rat juxtamedullary nephron microvascular preparation perfused in vitro with a cell-free media, addition of 20-HETE (1 nM-1 μM) to the bath reduced the diameter of proximal and distal portions of the afferent arterioles. At a concentration of 1 μM, the diameter of the proximal and distal portions of the afferent arteriole fell by 14 ± 1 and 16 ± 3% after 20-HETE. The response to 20-HETE (1 μM) was not altered by blockade of cyclooxygenase, lipoxygenase, and P-450 pathways. Blockade of the large-conductance Ca2+-activated K+ channel with tetraethylammonium (1 mM) reduced the diameter of afferent arterioles by 10% and blocked the vasoconstrictor response to 20-HETE (1 μM). These results indicate that 20- HETE is an endogenous constrictor of preglomerular arterioles and suggest a role for the P-450 4A2 enzyme in the regulation of renal vascular tone.

Original languageEnglish (US)
Pages (from-to)R217-R227
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume270
Issue number1 39-1
DOIs
StatePublished - 1996

Keywords

  • cytochrome P-450 4A
  • eicosanoids
  • kidney
  • potassium channels
  • vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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