Epoxyeicosatrienoic Acid Inhibition Alters Renal Hemodynamics During Pregnancy

Abstract

In this study we examined the expression of arachidonic acid epoxygenases (CYP2C and 2J)in different renal tissues isolated from pregnant rats. We also selectively inhibited EET production by administering N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH, 20 mg/kg/day, iv) to pregnant rats during days 14–17 of gestation and to age-matched virgin rats, and determined the effects on renal function. Western blot analysis showed significant increases in the expression of CYP2C11 (97%), CYP2C23 (21%), and CYP2J2 (164%) in the renal microvessels of Day 12 pregnant rats, as well as that CYP2C23 expression was increased in the proximal tubules throughout pregnancy. MSPPOH-treated pregnant rats had higher mean arterial pressure (MAP) (117 ± 3 versus 97 ± 2 mmHg, P<0.05, n=6) and renal vascular resistance (RVR) (21 ± 1 versus 16 ± 1 mmHg mL -1 min-1, P<0.05, n=6), but lower renal blood flow (RBF) (3.8 ± 0.1 versus 5.9 ± 0.3 mL min-1, P<0.05, n=6) and glomerular filtration rate (GFR) (1.6 ± 0.05 versus 1.9 ± 0.08 mL min-1, P<0.05, n=6). In contrast, MSPPOH treatment had no effect on renal hemodynamics in virgin rats. In pregnant rats, MSPPOH treatment caused selective inhibition of renal cortical EET production and decreased the expression of epoxygenases in the renal cortex, renal microvessels, and proximal tubules. Conclusion: This study demonstrates that CYP epxoygenases are altered in renal microvessels and proximal tubules during pregnancy in rats. Our findings demonstrate that the selective inhibition of EET production causes abnormal renal hemodynamics, and suggest that upregulation of renal vascular and tubular EETs contributes to the control of blood pressure and renal function during pregnancy.