Glomerular stereospecific synthesis and hemodynamic actions of 8,9-epoxyeicosatrienoic acid in rat kidney

Tetsuo Katoh, Kihito Takahashi, Jorge Capdevila, Armando Karara, J R Falck, Harry R. Jacobson, Kamal F. Badr

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Renal glomerular and cortical metabolism of endogenous arachidonic acid by cytochrome P-450 epoxygenase yields 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EET). Using gas chromatography-mass spectrometry, we measured the synthesis of 8,9-EET from an endogenous pool of arachidonic acid in normal rat kidney. The (8S,9R) isomer was favored over the (8R,9S) isomer in a ratio (%) of 59 to 41 in isolated glomeruli and 68 to 32 in cortex tissue. (8S,9R)- but not (8R,9S)-EET elicited dose-dependent vasoconstriction on intrarenal administration in the euvolemic Munich-Wistar rat. Micropuncture measurements of glomerular dynamics revealed that (8S,9R)-EET increased afferent arteriolar resistance (R(A)) leading to reductions in single-nephron plasma flow rate (Q̇(A)), net transcapillary hydraulic pressure difference (ΔP), and consequently single-nephron glomerular filtration rate (SNGFR). There was no significant change in the value of the glomerular capillary ultrafiltration coefficient (K(f)). In the presence of a cyclooxygenase inhibitor, indomethacin, the effects of 8,9-EET were reversed. R(A) fell leading to increases in Q̇(A) and ΔP, with resultant angmentation of SNGFR. Under these conditions, a modest reduction if K(f) was noted. Thus (8S,9R)-EET is a stereoselective renal vasoconstrictor, preferentially generated over its optical isomer, (8R,9S)-EET, suggesting that it is biologically relevant and implying specific structural requirements for EET receptor activation. The principal mechanism of action of 8,9-EET is preglomerular vasoconstriction. The vasoconstrictor effect of 8,9-EET is CO dependent.

Original languageEnglish (US)
Pages (from-to)F578-F586
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume261
Issue number4 30-4
StatePublished - Jan 1 1991

Keywords

  • cyclooxygenase
  • eicosanoids
  • glomerular filtration
  • renal blood flow

ASJC Scopus subject areas

  • Physiology

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