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ORIGINAL RESEARCH ARTICLE

Epoxyeicosatrienoic Acid Inhibition Alters Renal Hemodynamics During Pregnancy

Hui Huang^*,, Hsin-Hsin Chang^*, Yue Xu^*, D. Sudarshan Reddy, Juan Du^*, Yiqiang Zhou^*, Zheng Dong, John R. Falck and Mong-Heng Wang^*,1

^* Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912; Renal Department of the Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong Province, P. R. China; Department of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390; and Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912

To whom requests for reprints should be addressed at ¹ Department of Physiology, Medical College of Georgia, Augusta, GA 30912. E-mail: mwang{at}mail.mcg.edu

In this study we examined the expression of cytochrome P450 (CYP) 2C and CYP2J isoforms in renal proximal tubules and microvessels isolated from rats at different stages of pregnancy. We also selectively inhibited epoxyeicosatrienoic acid (EET) production by the administration of N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH 20 mg/kg/day iv) to rats during Days 14–17 of gestation and to age-matched virgin rats and determined the consequent effects on renal function. Western blot analysis showed that CYP2C11, CYP2C23, and CYP2J2 expression was significantly increased in the renal microvessels of pregnant rats on Day 12 of gestation. In the proximal tubules, CYP2C23 expression was significantly increased throughout pregnancy, while the expression of CYP2C11 was increased in early and late pregnancy and the expression of CYP2J2 was increased in middle and late pregnancy. MSPPOH treatment significantly increased pregnant rats’ mean arterial pressure, renal vascular resistance, and sodium balance but significantly decreased renal blood flow, glomerular filtration rate, and urinary sodium excretion, as well as fetal pups’ body weight and length. In contrast, MSPPOH treatment had no effect on renal hemodynamics or urinary sodium excretion in age-matched virgin rats. In pregnant rats, MSPPOH treatment also caused selective inhibition of renal cortical EET production and significantly decreased the expression of CYP2C11, CYP2C23, and CYP2J2 in the renal cortex, renal microvessels, and proximal tubules. These results suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy.

Key Words: cytochrome P450 • CYP2C • arachidonic acid • eicosanoids • epoxyeicosatrienoic acid • kidney • EET • pregnancy • renal hemodynamics

This article has been cited by other articles:

				H. Huang, C. Morisseau, J. Wang, T. Yang, J. R. Falck, B. D. Hammock, and M.-H. Wang Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats Am J Physiol Renal Physiol, July 1, 2007; 293(1): F342 - F349. [Abstract] [Full Text] [PDF]