Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats.
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.
Zhao
Xueying
X
Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA.
Dey
Aparajita
A
Romanko
Olga P
OP
Stepp
David W
DW
Wang
Mong-Heng
MH
Zhou
Yiqing
Y
Jin
Liming
L
Pollock
Jennifer S
JS
Webb
R Clinton
RC
Imig
John D
JD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000201:enzymology; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
C000717351:Cyp2c23 protein, rat; D007527:Isoenzymes; D012333:RNA, Messenger; C400322:cytochrome P-450 CYP2C subfamily; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D042926:Cytochrome P-450 CYP4A; D004851:Epoxide Hydrolases; D000109:Acetylcholine