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Previous studies have suggested that reserpine treatment may result in altered heart development. In order to more fully investigate this possibility, reserpine was administered s.c. at 0, 0.375, or 0.75 mg/kg/day to pregnant rats on gestation days 12-15. Maternal weight gain, as well as pup weight on postnatal day (PND) 1, was significantly reduced in a dose-dependent manner. Litter size was unaffected, but reserpine-treated dams had more dead pups than did control dams. On PND 1, litters were randomly standardized at ten pups each for analysis on PNDs 5, 8, 15, and 22. Pup body weight and heart weight were reduced in a dose-related manner at all ages measured. The decreased heart weights were probably due to decreases in cell number. Beta-adrenergic receptor concentration was significantly reduced only on PND 5, at the low reserpine dose, and was not considered to be a treatment effect. Prenatal reserpine exposure had no effect on levels of basal cardiac ornithine decarboxylase (ODC), an enzyme associated with growth and development. Cardiac ODC stimulation by insulin and isoproterenol also showed no effects of maternal reserpine treatment. The results suggest that maternal reserpine treatment may lead to adverse effects in the developing offspring.

Imipramine (IMI) was administered s.c. at 0, 5, or 10 mg/kg/day to pregnant rats on gestation days 8-20 to assess possible alterations in postnatal heart and brain development. Maternal weight gain was significantly reduced in a dose-response manner, but litter size and pup weight on postnatal day (PND) 1 were unaffected. On PND 1, litters were culled to 10 pups for analysis on PNDs 4/5, 7/8, 14/15, and 21/22. Pup body weight was not affected at any age measured, but heart weight was significantly reduced at 10 mg/kg IMI on PNDs 4/5 and 7/8. Brain weight was increased in a dose-related pattern on PNDs 4/5 and 7/8 and was significantly higher at 5 mg/kg IMI on PND 14/15. No significant effect was observed in heart or brain protein and DNA content or in cardiac beta-adrenergic receptor concentration. Prenatal IMI exposure had no effect on basal cardiac ornithine decarboxylase (ODC), an enzyme associated with growth and development, but basal brain ODC was lower at 5 mg/kg IMI at all ages measured. Cardiac ODC stimulation by insulin was unaffected by prenatal exposure to IMI, but isoproterenol-stimulated ODC was increased on PND 21/22 at 5 mg/kg IMI. In conclusion, the IMI-related changes in several parameters suggest that when maternal IMI treatment is used, alterations in postnatal heart and brain development must be considered as possible outcomes.

Maternal propranolol (PRO) treatment has previously been associated with adverse effects on the fetus and neonate. In the present study, pregnant rats were treated with PRO (25 or 50 mg/kg/day s.c.) on gestation days 8-20 to assess its possible effects on the developing heart. Maternal weight gain and pup weight on postnatal day (PND) 1 were reduced in a dose-dependent manner; litter size was unaffected. Pup body weight and heart weight both showed a dose-related decrease at all ages tested (PNDs 5/6, 8/9, 15/16, and 22/23). Since heart protein, but not DNA, was similarly reduced, the decrease seen in heart weight most likely reflects a decrease in cell size instead of cell number. Basal ornithine decarboxylase (ODC), an enzyme associated with growth and development, was unaffected by maternal PRO treatment. Insulin and isoproterenol stimulation of ODC, suggested markers for testing the function of the sympathetic pathway to the heart and of the heart's ODC response system, respectively, also showed no PRO-related response. In conclusion, prenatal PRO exposure resulted in reduced body weight, heart weight, and heart protein, but had little effect on heart DNA or ODC activity. Since PRO treatment also reduced maternal weight gain, the adverse effects seen in the pups may be due to generalized PRO toxicity. The results suggest that when high PRO doses were used clinically, the careful monitoring of maternal weight gain during pregnancy might be useful in predicting adverse fetal effects.