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Am J Physiol Renal Physiol 286: F720-F726, 2004. First published December 9, 2003; doi:10.1152/ajprenal.00165.2003
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Vascular localization of soluble epoxide hydrolase in the human kidney

Zhigang Yu,1 Benjamin B. Davis,2 Christophe Morisseau,3 Bruce D. Hammock,3 Jean L. Olson,4 Deanna L. Kroetz,1 and Robert H. Weiss2,5

Departments of 1Biopharmaceutical Sciences and 4Anatomic Pathology, University of California San Francisco, San Francisco 94143; Division of Nephrology, Departments of 2Internal Medicine and 3Entomology and Cancer Center, University of California Davis, Davis 95616;and 5Department of Veterans' Affairs Medical Center, Mather, California 95655

Submitted 25 April 2003 ; accepted in final form 5 December 2003

Epoxyeicosatrienoic acids are cytochrome P-450 metabolites of arachidonic acid with multiple biological functions, including the regulation of vascular tone, renal tubular transport, cellular proliferation, and inflammation. Epoxyeicosatrienoic acids are converted by soluble epoxide hydrolase into the corresponding dihydroxyeicosatrienoic acids, and epoxyeicosatrienoic acid hydration is regarded as one mechanism whereby their biological effects are eliminated. Previous animal studies indicate that soluble epoxide hydrolase plays an important role in the regulation of renal eicosanoid levels and systemic blood pressure. To begin to elucidate the mechanism of these effects, we determined the cellular localization of soluble epoxide hydrolase in human kidney by examining biopsies taken from patients with a variety of non-end-stage renal diseases, as well as those without known renal disease. Immunohistochemical staining of acetone-fixed kidney biopsy samples revealed that soluble epoxide hydrolase was preferentially expressed in the renal vasculature with relatively low levels in the surrounding tubules. Expression of soluble epoxide hydrolase was evident in renal arteries of varying diameter and was localized mostly in the smooth muscle layers of the arterial wall. Western blot analysis and functional assays confirmed the expression of soluble epoxide hydrolase in the human kidney. There were no obvious differences in soluble epoxide hydrolase expression between normal and diseased human kidney tissue in the samples examined. Our results indicate that soluble epoxide hydrolase is present in the human kidney, being preferentially expressed in the renal vasculature, and support an essential role for this enzyme in renal hemodynamic regulation and its potential utility as a target for therapeutic intervention.

microvasculature; epoxyeicosatrienoic acids; dihydroxyeicosatrienoic acids


Address for reprint requests and other correspondence: D. L. Kroetz, Dept. of Biopharmaceutical Sciences, Univ. of California San Francisco, 513 Parnassus, Box 0446, San Francisco, CA 94143-0446 (E-mail: deanna{at}itsa.ucsf.edu).




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