Sildenafil citrate improves perinatal outcome in fetuses from pre‐eclamptic rats

Abstract

Objective To evaluate perinatal outcome after sildenafil citrate (SC) administration at the onset of pregnancy in a rat preeclampsia model.Design In vivo animal experimental study.Setting Fundació n IVI-Instituto Universitario IVI, Valencia, Spain.SampleControl and pre-eclampsia-induced pregnant Wistar rats exposed to chronic SC administration.Methods We evaluated the use of SC, which was tested as a potential therapeutic tool to maintain vasodilatation in complicated pregnancies. We have demonstrated previously that SC shows a hypotensive selective effect in normal rat pregnancies when compared with nonpregnant animals.Main outcome measures Maternal blood pressure, weight and mortality during pre-and postnatal development, maternal blood cellularity and haemodynamic changes with maternal and fetal Doppler quantitative indices.Results SC restores normal values of blood pressure, cell count and proteinuria for maternal syndrome. In offspring, SC improves weight gain and increases survival rates without fetotoxic effects. According to the haemodynamic results, SC has a significant effect on the resistance index in the uterine artery in pre-eclamptic animals, as it restores normal values to correlate with an increase in fetal perfusion through the ductus venosus.Conclusions These results suggest that SC administration during pregnancy may have a potential benefit for the treatment of hypertension during pregnancy by reversing the maternal effects of pre-eclampsia and by improving uteroplacental and fetal perfusion.

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

“…Furthermore, sildenafil treatment significantly decreased the uterine artery resistance index of sFlt1 mice with normalization of blood flow to the gravid uterus ( Figure 5G; P < 0.05). These data are consistent with recent publications suggesting the efficacy of sildenafil in other models of fetal growth restriction or preeclampsia (31)(32)(33)(34), and support the potential to use sildenafil as a novel therapy to alleviate signs and symptoms of preeclampsia. However, the safety and potential benefit of this therapy to the fetus have not been explored.…”

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling

“…Phosphodiesterase type-5 messenger RNA is expressed in the uterus and placenta (14). Interestingly, recent studies have shown that sildenafil can be used successfully to correct a thin endometrium and reduce recurrent implantation failure (15,16), and therapeutically for intrauterine growth restriction (IUGR) and pre-eclampsia (17,18). Others have refuted the suggested benefits of sildenafil as a treatment for preeclampsia (19,20), but the intervention might have been applied too late to reverse endothelial damage and placental dysfunction.…”

Sildenafil Treatment Ameliorates the Maternal Syndrome of Preeclampsia and Rescues Fetal Growth in the Dahl Salt–Sensitive Rat

“…Sildenafil treatment was found to improve fetal growth and normalize umbilical artery Doppler waveforms in the preeclamptic catechol-O-Methyl Transferase knockout (COMT −/− ) mouse model 5 . However, sildenafil administration in the L-NAME model of intrauterine growth restriction and preeclampsia have yielded mixed results with one study reporting that sildenafil treatment resulted in a decrease in pup weight 10 and another that demonstrated sildenafil improved both maternal and fetal outcomes 11 . Sildenafil treatment was not able to prolong pregnancy in preeclamptic women in a small clinical trial 8 ; however, this may have been due to late administration and suboptimal dosing.…”