Sildenafil citrate improves fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats

Eur J Obstet Gynecol Reprod Biol. 2010 Mar;149(1):22-6. doi: 10.1016/j.ejogrb.2009.11.005. Epub 2010 Jan 19.

Abstract

Objectives: This study aimed to investigate the effects of sildenafil citrate on various fetal and physiological parameters, including fetal mortality, number of pups, placental weights and micro-albuminuria in pregnant, L-NAME treated Sprague-Dawley rats.

Study design: Twenty-four pregnant female Sprague-Dawley rats were divided into 3 groups (n=8). In the L-NAME treated group (PRE), l-NAME (0.3 g/l, drinking water) was used to induce pre-eclampsia-like symptoms on day 1 of the experiment. The experimental group (SCT) also received L-NAME (0.3 g/l, drinking water) on day 1 of the experiment. However, sildenafil citrate (10 mg/kg, s.c., daily) was administered as the test compound from day 7 until day 19. The experimental control (CON) did not receive either L-NAME or sildenafil citrate. L-NAME administration was discontinued in both the PRE and the SCT groups on day 19 of the experiment and the animals were given access to normal drinking water ad libitum. All the animals were sacrificed on day 20, at which time a laparotomy was performed and the various fetal parameters measured. On day 0 and day 20, blood pressure measurements were recorded non-invasively and protein estimations in 24h urine samples were conducted.

Results: Sildenafil citrate decreased fetal mortality and protein excretion and further demonstrated a trend toward increasing birth and placental weights in pregnant, L-NAME treated, Sprague-Dawley rats. In addition, sildenafil citrate administration ameliorated the amplification of the L-NAME induced hypertension in the SCT group.

Conclusion: We speculate that sildenafil citrate by potentiating the effects of nitric oxide in vivo improves uterine artery blood flow resulting in improved fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Female
  • Fetal Death / prevention & control*
  • NG-Nitroarginine Methyl Ester
  • Piperazines / pharmacology*
  • Pre-Eclampsia / chemically induced
  • Pre-Eclampsia / drug therapy*
  • Pregnancy
  • Pregnancy Outcome
  • Purines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sildenafil Citrate
  • Sulfones / pharmacology*
  • Vasodilator Agents / pharmacology

Substances

  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate
  • NG-Nitroarginine Methyl Ester