Onset of the Constrictive Effect of Indomethacin on the Ductus arteriosus in Fetal Rats

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Abstract
The time of onset of the constrictive effect of indomethacin on the ductus arteriosus (DA) in fetal rats was assessed by measurement of the caliber of the DA after maternal treatment with indomethacin on days 19–21 of gestation. The day following overnight mating was regarded as day 0 of gestation. Observation was performed by direct exposure of the DA by hand shaving of intact frozen fetuses. On days 20 and 21 the DA was significantly constricted 3 h after maternal treatment with 1 mg/kg of indomethacin. When the DA was examined at 19½ and 19¾ days of gestation (3 h after indomethacin exposure), it was significantly constricted at 19¾ days but not at 19½ days. Higher doses of indomethacin (10 and 100 mg/kg) induced a significant constriction of the DA at day 19½, but not at the beginning of the same day (1.00 a.m.). These results suggest that the onset of the susceptibility of the DA to the constrictive effect of indomethacin occurs in the first half of day 19 of gestation.

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