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1 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA
2 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA; Department of Physiology, Medical College of Georgia, Augusta, GA, USA
3 Department of Physiology, Medical College of Georgia, Augusta, GA, USA
4 Vascular Biology Center, Medical College of Georgia, Augusta, GA, USA; Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, USA
* To whom correspondence should be addressed. E-mail: jdimig{at}mail.mcg.edu.
Previous studies suggest that epoxyeicosatrienoic acids (EETs) are vasodilators of the mesenteric artery; however, the production and regulation of EETs in the mesenteric artery remains unclear. The current study was designed (1) to determine which epoxygenase isoforms may contribute to formation of EETs in mesenteric arteries; and (2) to determine the regulation of mesenteric artery cytochrome P450 (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 expression 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 to lean Zucker rats, mesenteric arterial CYP2C11 and CYP2J protein were decreased by 38% and 43%, respectively, in obese Zucker rats. In contrast, soluble epoxide hydrolase (sEH) mRNA and protein expression were significantly increased in obese Zucker rat mesenteric arteries. In addition, NO-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 sEH are associated with impaired mesenteric artery dilator function in obese Zucker rats.
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