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).


CONCLUSIONS
Exposure to sildenafil in a non-hypoxic setting 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.
Refuerzo
Jerrie S
JS
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Wayne State University, Detroit, MI 48201, USA. jrefuerz@med.wayne.edu
Sokol
Robert J
RJ
Aranda
Jacob V
JV
Hallak
Mordechai
M
Hotra
John W
JW
Kruger
Michael
M
Sorokin
Yoram
Y
D000818:Animals; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D000860:Hypoxia / Q000150:complications; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D011248:Pregnancy Complications; D011687:Purines; D051381:Rats; D000068677:Sildenafil Citrate; D013450:Sulfones
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D006152:Cyclic GMP