AJP - Endocrinology and Metabolism, Vol 258, Issue 2 E269-E274, Copyright © 1990 by American Physiological Society

ARTICLES

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

W. L. Henrich, J. R. Falck and W. B. Campbell
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.

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 less than 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 less than 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.

This article has been cited by other articles:

				I. Fleming Cytochrome P450 and Vascular Homeostasis Circ. Res., October 26, 2001; 89(9): 753 - 762. [Abstract] [Full Text] [PDF]

				J. D. Imig Eicosanoid regulation of the renal vasculature Am J Physiol Renal Physiol, December 1, 2000; 279(6): F965 - F981. [Abstract] [Full Text] [PDF]

				J. H. Capdevila, J. R. Falck, and R. C. Harris Cytochrome P450 and arachidonic acid bioactivation: molecular and functional properties of the arachidonate monooxygenase J. Lipid Res., February 1, 2000; 41(2): 163 - 181. [Abstract] [Full Text]

				J. Ma, W. Qu, P. E. Scarborough, K. B. Tomer, C. R. Moomaw, R. Maronpot, L. S. Davis, M. D. Breyer, and D. C. Zeldin Molecular Cloning, Enzymatic Characterization, Developmental Expression, and Cellular Localization of a Mouse Cytochrome P450 Highly Expressed in Kidney J. Biol. Chem., June 18, 1999; 274(25): 17777 - 17788. [Abstract] [Full Text] [PDF]

				X. Fang, T. L. Kaduce, N. L. Weintraub, M. VanRollins, and A. A. Spector Functional Implications of a Newly Characterized Pathway of 11,12-Epoxyeicosatrienoic Acid Metabolism in Arterial Smooth Muscle Circ. Res., October 1, 1996; 79(4): 784 - 793. [Abstract] [Full Text]