Systemic Sildenafil does not affect maternal hemodynamics or fetal growth in rat pregnancy

Abstract

It has been hypothesized that the PDE5 inhibitor sildenafil (SILD) may be useful in the treatment of hypertension during pregnancy. However, we previously showed that increased renal inner medullary PDE5 is involved in the Na retention of pregnancy. The purpose of this study was to determine the effects of oral SILD treatment on maternal plasma volume, Na balance and fetal growth during rat pregnancy. Rats received SILD (10 mg/kg/day (SILD10, n=5) or 50 mg/kg/day (SILD50, n=6)) in food or control diet (CON, n=7) on days 4–20 of pregnancy. On days 14–19, rats were housed in metabolic cages for collection of urine and measurement of Na intake, and hemodynamic and fetal measurement were taken on day 20. Both doses of SILD increased plasma cGMP concentrations (Table, * p<0.05 vs CON); however, sildenafil treatment had no effect on mean arterial pressure (MAP), weight, hematocrit (HCT) or plasma volume (PV). The SILD10 dose slightly reduced sodium retention over the 5 day period, but glomerular filtration rate (creatinine clearance, CCr) was not significantly changed by either SILD treatment. The pup number and size were similar among the groups. Therefore, these studies suggest that oral (systemic) SILD may be safe during pregnancy. The effects of SILD on hypertension during pregnancy should be examined separately.