Abstract
Objective To assess the effect of sildenafil citrate in a rat model of Nω-nitro-l-arginine methyl ester (L-NAME)-induced intrauterine growth restriction (IUGR).
Study Design An in vivo experimental study was conducted where 40 pregnant Sprague-Dawley rats
were randomly assigned to receive either: (1) control, (2) L-NAME 50 mg/kg/d by gavage
(days 14 to 19), (3) L-NAME and sildenafil 15 mg/kg/d by gavage, or (4) sildenafil
(days 14 to 21). On day 21, a hysterotomy was performed and all fetuses (live and
dead) were counted, examined, and weighed. The primary outcome measure was the difference
in pup birth weight.
Results The median number of live pups per dam was 11.5 (range: 1 to 15), 13.5 (2 to 17),
13.5 (7 to 16), and 11.5 (4 to 17) in controls, L-NAME, sildenafil, and combined drug
groups, respectively (p = 0.02). Rats treated with L-NAME had a significantly higher number of stillbirths
compared with control (p = 0.013) and sildenafil (p = 0.008) groups. L-NAME reduced pup birth weight compared with controls (4.53 ± 1.49
versus 5.65 ± 1.63 g, p < 0.001); this effect was more pronounced in the L-NAME and sildenafil groups (3.37 ± 1.25 g,
p < 0.001).
Conclusion Our data indicate that sildenafil citrate does not ameliorate L-NAME-induced IUGR,
and in the doses utilized in this study might even have a synergistic negative effect
on pup birth weight.
Keywords
intrauterine growth restriction - preeclampsia - rat model - sildenafil citrate -
L-NAME