Pravastatin attenuates hypertension and angiogenic imbalance in placental ischemia induced hypertension in the rat

Abstract

Preeclampsia is a pregnancy‐specific condition characterized by an imbalance of circulating angiogenic factors and new onset hypertension. Although current treatment options are very limited, recent studies suggest pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin administration would increase VEGF and reduce arterial pressure (AP) in rats with reduced utero‐placental perfusion pressure (RUPP)‐induced hypertension. On day 14 of pregnancy (21‐term), silver clips were placed on the inferior abdominal aorta and ovarian arteries to generate RUPP‐hypertension. Pravastatin (RUPP+P) was administered i.p. (1 mg/kg/day) through day 19. On day 19 AP was measured via catheter and conceptus data recorded. Blood pressure was increased (P<0.05) in RUPP compared to normal pregnant (NP) dams and pravastatin ameliorated this difference (118±3 vs 91±2 vs 109±2 mmHg). Fetal weight was decreased (P<0.05) in RUPP dams compared to NP controls, but was not improved in RUPP+P (2.07±0.1 vs 2.44±0.05 vs 2.23±0.08 g). RUPP decreased plasma VEGF when compared to NP dams and this was attenuated by pravastatin (759.8±52.3 vs 924.1±43.6 vs 969.5±85.3 pg/mL; P<0.05). Pravastatin did not alter AP, fetal weight, or plasma VEGF in NP dams compared to NP controls. The present data suggest pravastatin may be effective in treating placental ischemia induced hypertension.