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A recent in vitro study showed that sildenafil, a type 5 phosphodiesterase inhibitor, dilated the constricted ductus arteriosus of neonatal rabbits. We studied the in vivo ductus-dilating effects of sildenafil in fetal and neonatal rats. Ductus diameters were measured with whole-body freezing and cutting on a freezing microtome. Indomethacin (10 mg/kg) constricted the fetal ductus severely at 4 and 8 h after orogastric administration to the dams. Sildenafil, administered orogastrically and simultaneously with indomethacin, dilated the near-term fetal [21 fetal days (FD)] ductus constricted by indomethacin completely with 1 mg/kg at 8 h after administration. The preterm fetal ductus was more sensitive to sildenafil at 19FD. The ductus constricted rapidly after birth, and the ductal diameter was only 10% of the fetal diameter at 1 h after birth. The ductus-dilating effect of sildenafil was studied by i.p. injection at 1 h after birth, and the ductus diameter was studied 30 and 60 min later. Sildenafil dilated the neonatal constricted ductus moderately with a massive dose (100 mg/kg) and only minimally with 1 mg/kg. In conclusion, sildenafil, a type 5 phosphodiesterase inhibitor, dilated the constricted fetal ductus completely at 8 h with 1 mg/kg in the near-term fetus and completely with a smaller dose (0.1 mg/kg) in the preterm fetus. However, sildenafil dilated the neonatal constricted ductus only moderately with large doses and minimally with 1 mg/kg. Probably, sildenafil is useful clinically for treating idiopathic and secondary fetal ductal constriction and not useful for dilation of the neonatal constricted ductus.

In Vivo Dilation of Fetal and Neonatal Ductus Arteriosus by Inhibition of Phosphodiesterase-5 in Rats