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Haemodynamic effects of long-term administration of sildenafil in normotensive pregnant and non-pregnant rats

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Abstract:

Please cite this paper as: Pellicer B, Herraiz S, Cauli O, Rodrigo R, Asensi M, Cortijo J, Serra V, Morcillo E, Felipo V, Simón C, Pellicer A. Haemodynamic effects of long-term administration of sildenafil in normotensive pregnant and non-pregnant rats. BJOG 2011;118:615–623. Objective 

To determine the effects of chronic administration of sildenafil citrateon healthy pregnant rats. Design 

In vivo animal experimental study. Setting 

Fundación IVI–Instituto Universitario IVI, Valencia, Spain. Sample 

Pregnant and non-pregnant Wistarrats exposed to chronic administration of sildenafil. Methods 

Placental cross-barrier and feto-maternal relationship levels, maternal blood pressure, and haemodymamic effects on uterine arteries were evaluated. The effect of growth on weight and fetal tissues, and on perinatal outcome, was investigated. Main outcome measures 

Maternal blood pressure, blood viscosity, vascular indices of uterine arteries and fetal ductus venosus, plasmatic levels of sildenafil, embryo/fetal and litter weights, perinatal/postnatal survival rates. Results 

Sildenafil citrate crossed the placenta. The maternal and fetal levels of sildenafil, and its metabolite desmethyl-sildenafil, demonstrated a positive linear correlation in treated pregnant animals versus controls; a selective maternal hypotensive effect without changes in uterine vascular resistance was noted on days E8 and E11 (embryonic day). The lower pulsatility index of the ductus venosus on day E18 suggests fetal overflow at the end of the pregnancy. Effects on offspring were placental and liver enlargement, and increased fetal weight gain in the second half of pregnancy (irrespective of liver enlargement) and at birth. Perinatal and postnatal survival rates in the sildenafil group remained unaltered. No haemodynamic effects were evident in non-pregnant animals. Conclusions 

In normotensive rats, sildenafil appears to have a selective effect at the onset of pregnancy, implying increased fetal blood supply, and increased fetal weight, and placental and liver enlargement, but no increased perinatal mortality.

Keywords: Blood pressure; ductus venosus; pregnancy; sildenafil

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1471-0528.2010.02839.x

Affiliations: 1:  Hospital de Manises, Manises, Spain 2:  Fundación IVI, University of Valencia, Valencia, Spain 3:  Neurobiology Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain 4:  Department of Physiology, Valencia University School of Pharmacy, Burjassot, Spain 5:  Department of Pharmacology, Valencia University School of Medicine, Valencia, Spain

Publication date: April 1, 2011

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