Sildenafil citrate and fetal outcome in pregnant rats

Objective: To determine the effects of sildenafil citrate on fetal growth in maternal rats exposed to hypoxia. Methods: Timed pregnant rats were randomized to either hypoxia or control on gestational days (GD) 18-20, and received either sildenafil (45 mg/kg) orally every 12 h on GD 18-21 or an equal volume of sterile water. Fetal pups were retrieved by laparotomy on GD 21. Pup weight and length were evaluated and cGMP measured in maternal and fetal blood. Results: In the non-hypoxic rats, sildenafil exposure was associated with a decrease in size (4.75 ± 0.43 vs. 5.11 ± 0.34 g, p = 0.00). In contrast, in the hypoxic rat model, sildenafil exposure was associated with increased size of the offspring (5.48 ± 0.45 vs. 5.16 ± 0.36 g, p = 0.016). Maternal cGMP levels were increased in the presence of both sildenafil and hypoxia (23.0 ± 10.5 vs. 15.6 ± 2.7 pmol/ml, p = 0.001). Conclusion: Exposure to sildenafil in a non-hypoxic seting results in a decrease in fetal size. Sildenafil in the presence of a stimulus, hypoxia, will lead to increased fetal size. These results suggest that sildenafil may have some influence on fetal growth. How these effects occur and by what mechanism remain to be determined.