Faculty Collaboration Database

Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 2005 Jan;288(1):R188-96

Date

09/04/2004

Pubmed ID

15345471

DOI

10.1152/ajpregu.00018.2004

Scopus ID

2-s2.0-19944424115 (requires institutional sign-in at Scopus site)   77 Citations

Abstract

Previous studies suggest that epoxyeicosatrienoic acids (EETs) are vasodilators of the mesenteric artery; however, the production and regulation of EETs in the mesenteric artery remain unclear. The present study was designed 1) to determine which epoxygenase isoform may contribute to formation of EETs in mesenteric arteries and 2) to determine the regulation of mesenteric artery cytochrome P-450 (CYP) enzymes in obese Zucker rats. Microvessels were incubated with arachidonic acid, and CYP enzyme activity was determined. Mesenteric arteries demonstrate detectable epoxygenase and hydroxylase activities. Next, protein and mRNA expressions were determined in microvessels. Although renal microvessels express CYP2C23 mRNA and protein, mesenteric arteries lacked CYP2C23 expression. CYP2C11 and CYP2J mRNA and protein were expressed in mesenteric arteries and renal microvessels. In addition, mesenteric artery protein expression was evaluated in lean and obese Zucker rats. Compared with lean Zucker rats, mesenteric arterial CYP2C11 and CYP2J proteins were decreased by 38 and 43%, respectively, in obese Zucker rats. In contrast, soluble epoxide hydrolase mRNA and protein expressions were significantly increased in obese Zucker rat mesenteric arteries. In addition, nitric oxide-independent dilation evoked by acetylcholine was significantly attenuated in mesenteric arteries of obese Zucker rats. These data suggest that the main epoxygenase isoforms expressed in mesenteric arteries are different from those expressed in renal microvessels and that decreased epoxygenases and increased soluble epoxide hydrolase are associated with impaired mesenteric artery dilator function in obese Zucker rats.

Author List

Zhao X, Dey A, Romanko OP, Stepp DW, Wang MH, Zhou Y, Jin L, Pollock JS, Webb RC, Imig JD

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

Acetylcholine
Animals
Arachidonic Acid
Cytochrome P-450 CYP4A
Cytochrome P-450 Enzyme System
Epoxide Hydrolases
Gene Expression Regulation, Enzymologic
Isoenzymes
Kidney
Male
Mesenteric Arteries
Obesity
RNA, Messenger
Rats
Rats, Sprague-Dawley
Rats, Zucker
Vasodilation