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

2004; Lippincott Williams & Wilkins; Volume: 43; Issue: 3 Linguagem: Inglês

10.1161/01.hyp.0000117721.83371.9f

1524-4563

María T. Llinás, Barbara T. Alexander, Maria F. Capparelli, Mairéad A. Carroll, Joey P. Granger,

Pregnancy and preeclampsia studies

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.