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(Hypertension. 2004;43:623.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Cytochrome P-450 Inhibition Attenuates Hypertension Induced by Reductions in Uterine Perfusion Pressure in Pregnant Rats

Maria T. Llinás; Barbara T. Alexander; Maria F. Capparelli; Mairead A. Carroll; Joey P. Granger

From Department of Physiology and Biophysics (M.T.L., B.T.A., J.P.G.), Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, and Department of Pharmacology (M.F.C., M.A.C.), New York Medical College, Valhalla.

Correspondence to Dr Joey P. Granger, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. E-mail jgranger{at}physiology.umsmed.edu

The present study tested the hypothesis that cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) are involved in mediating hypertension and renal vasoconstriction during chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. 1-aminobenzotriazole (ABT), a CYP enzyme inhibitor (25 mg/kg per day), or vehicle (saline 0.9%) was administered for 7 days to normal pregnant (NP) rats and to pregnant rats with chronic RUPP. RUPP rats infused with vehicle showed significantly (P<0.01) higher mean arterial pressure (MAP) (130±2 versus 106±1 mm Hg), renal vascular resistance (RVR) (22.6±1.8 versus 16.3±1.1 mm Hg/mL per minute) and lower (P<0.05) glomerular filtration rate (GFR) (1.6±0.1 versus 2.3±0.1 mL/min) than NP rats. ABT decreased (P<0.01) MAP in RUPP rats (111±1 mm Hg), whereas it had no effect in NP rats (108±2 mm Hg). CYP inhibition also attenuated the differences in renal hemodynamics observed between NP and RUPP rats. After treatment with ABT, RVR and GFR were similar in RUPP rats (19.3±1.5 mm Hg/mL per minute and 2.0±0.2 mL/min, respectively) and NP rats (16.3±2.4 mm Hg/mL per minute and 2.4±0.2 mL/min). The effects of CYP enzymes inhibitor in RUPP rats were associated with a reduction (P<0.05) of 20-HETE formation (32%) and a decreased (P<0.05) expression (33%) of CYP4A protein in renal cortex. In contrast, renal epoxygenase activity did not change in these animals. These results suggest that 20-HETE contributes to hypertension and renal vasoconstriction induced by chronic RUPP in pregnant rats.

Key Words: preeclampsia • CYP-450 • hypertension

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