Faculty Collaboration Database

Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases. Am J Physiol Renal Physiol 2005 Sep;289(3):F496-503

Date

08/12/2005

Pubmed ID

16093425

DOI

10.1152/ajprenal.00350.2004

Scopus ID

2-s2.0-23944460748 (requires institutional sign-in at Scopus site)   199 Citations

Abstract

Renal epoxygenase metabolites are involved in blood flow regulation and long-term blood pressure control. One feature of renal and cardiovascular diseases is the inability of the kidney to properly increase epoxyeicosatrienoic acid (EET) levels. Others (Busse R, Edwards G, Félétou M, Fleming I, Vanhoutte PM, and Weston AH. Trends Phamacol Sci 23: 374-380, 2002; Campbell WB, Gebremedhin D, Pratt PF, and Harder DR. Circ Res 78: 415-423, 1996; Capdevila JH and Falck JR. Biochem Biophys Res Commun 285: 571-576, 2001; Roman RJ. Physiol Rev 82: 131-185, 2002; Zeldin DC. J Biol Chem 276: 36059-36062, 2001) and we (Imig JD, Falck JR, Wei S, and Capdevila JH. J Vasc Res 38: 247-255, 2001; Imig JD, Zhao X, Capdevila JH, Morisseau C, and Hammock BD. Hypertension 39: 690-694, 2002; Zhao X, Pollock DM, Inscho EW, Zeldin DC, and Imig JD. Hypertension 41: 709-714, 2003; Zhao X, Pollock DM, Zeldin DC, and Imig JD. Hypertension 42: 775-780, 2003) have provided compelling evidence that cytochrome P-450-derived EETs have antihypertensive properties and are endothelially derived hyperpolarizing factors (EDHFs) in the kidney. EETs also possess anti-inflammatory actions that could protect the kidney vasculature from injury during renal and cardiovascular diseases. A tactic that has been used to increase EET levels has been inhibition of the soluble epoxide hydrolase enzyme. Epoxide hydrolase inhibitors have been demonstrated to be antihypertensive and renal protective. Thus the renal and cardiovascular protective actions of increasing epoxygenase levels could be translated to therapies for preventing end-organ damage.

Author List

Imig JD

MESH terms used to index this publication - Major topics in bold

Animals
Epoxide Hydrolases
Humans
Kidney
Kidney Diseases
Oxidoreductases