Inhibition of renin release by 14,15-epoxyeicosatrienoic acid in renal cortical slices

W. L. Henrich, J. R. Falck, W. B. Campbell

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The effects of products of the cytochrome P-450 epoxygenase pathway of arachidonate metabolism on renin have not been previously examined. Initial high-performance liquid chromatography and gas chromatography-mass spectrometry studies documented the synthesis of four epoxyeicosatrienoic acid (EET) regioisomers of epoxygenase in superficial cortical slices from male Sprague-Dawley rats. Each regioisomer was tested for effects on both isoproterenol (ISO)-stimulated and basal renin secretion from cortical slices. ISO increased renin release significantly (169%, P < 0.01) in all incubations; 14,15-EET (10-6 M) significantly reduced this increase in stimulated renin release to 47%. The 5,6-, 8,9-, and 11,12-EETs did not significantly affect renin release. Basal renin release was not affected by any of the four EETs. To examine the mechanism of this inhibitory action, the effects of 14,15-EET on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 5'-cyclic monophosphate (cGMP) concentrations were measured. Tissue cAMP concentrations were sharply increased (4.75-fold, P < 0.001) by ISO; 14,15-EET did not blunt this increase significantly. ISO and 14,15-EET did not affect tissue cGMP concentrations. Incubation of [14C]EET with cortical slices resulted in only 10% conversion of the 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (DHET) (diol) after 90 min; no other metabolites were observed. The 14,15 DHET did not alter either basal or stimulated renin release. These studies document the synthesis of EETs in rat kidney and demonstrate a direct effect of the 14,15-EET to inhibit stimulated renin release. This inhibitory action occurs without an effect on tissue cAMP or cGMP concentrations.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume258
Issue number2 21-2
StatePublished - 1990

Fingerprint

Renin
Kidney
Guanosine Monophosphate
Isoproterenol
Guanosine
Cyclic GMP
Tissue
Rats
Acids
14,15-epoxy-5,8,11-eicosatrienoic acid
High performance liquid chromatography
Metabolites
Metabolism
Gas chromatography
Cyclic AMP
Gas Chromatography-Mass Spectrometry
Cytochrome P-450 Enzyme System
Mass spectrometry
Sprague Dawley Rats
High Pressure Liquid Chromatography

Keywords

  • adenosine 3',5'-cyclic monophosphate
  • cytochrome P 450
  • guanosine 3',5'-cyclic monophosphate
  • isoproterenol

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

Inhibition of renin release by 14,15-epoxyeicosatrienoic acid in renal cortical slices. / Henrich, W. L.; Falck, J. R.; Campbell, W. B.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 258, No. 2 21-2, 1990.

Research output: Contribution to journalArticle

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abstract = "The effects of products of the cytochrome P-450 epoxygenase pathway of arachidonate metabolism on renin have not been previously examined. Initial high-performance liquid chromatography and gas chromatography-mass spectrometry studies documented the synthesis of four epoxyeicosatrienoic acid (EET) regioisomers of epoxygenase in superficial cortical slices from male Sprague-Dawley rats. Each regioisomer was tested for effects on both isoproterenol (ISO)-stimulated and basal renin secretion from cortical slices. ISO increased renin release significantly (169{\%}, P < 0.01) in all incubations; 14,15-EET (10-6 M) significantly reduced this increase in stimulated renin release to 47{\%}. The 5,6-, 8,9-, and 11,12-EETs did not significantly affect renin release. Basal renin release was not affected by any of the four EETs. To examine the mechanism of this inhibitory action, the effects of 14,15-EET on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 5'-cyclic monophosphate (cGMP) concentrations were measured. Tissue cAMP concentrations were sharply increased (4.75-fold, P < 0.001) by ISO; 14,15-EET did not blunt this increase significantly. ISO and 14,15-EET did not affect tissue cGMP concentrations. Incubation of [14C]EET with cortical slices resulted in only 10{\%} conversion of the 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (DHET) (diol) after 90 min; no other metabolites were observed. The 14,15 DHET did not alter either basal or stimulated renin release. These studies document the synthesis of EETs in rat kidney and demonstrate a direct effect of the 14,15-EET to inhibit stimulated renin release. This inhibitory action occurs without an effect on tissue cAMP or cGMP concentrations.",
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