Haemodynamic effects of long-term administration of sildenafil in normotensive pregnant and non-pregnant rats.
OBJECTIVE
To determine the effects of chronic administration of sildenafil citrate on healthy pregnant rats.


METHODS
In vivo animal experimental study.


METHODS
Fundación IVI-Instituto Universitario IVI, Valencia, Spain.


METHODS
Pregnant and non-pregnant Wistar rats 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.


METHODS
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.
Hospital de Manises, C/Roses s/n, Manises, Valencia, Spain. pellicer_beg@gva.es
B
B
Pellicer
S
S
Herraiz
O
O
Cauli
R
R
Rodrigo
M
M
Asensi
J
J
Cortijo
V
V
Serra
E
E
Morcillo
V
V
Felipo
C
C
Simón
A
A
Pellicer
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001809:Blood Viscosity / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000098:blood supply; D009929:Organ Size / Q000187:drug effects; D010879:Piperazines / Q000097:blood / Q000494:pharmacology*; D010920:Placenta / Q000033:anatomy & histology / Q000187:drug effects; D011247:Pregnancy; D011687:Purines / Q000097:blood / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000097:blood / Q000494:pharmacology*; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal; D014599:Uterus / Q000098:blood supply; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate