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Effect of prenatal propranolol exposure on development of the postnatal rat heart
Insights
Maternal propranolol (PRO) treatment during pregnancy reduced pup body weight and heart weight in a dose-dependent manner. These effects may stem from generalized toxicity, highlighting the need for careful maternal weight monitoring.
Area of Science:
- Pharmacology
- Developmental Biology
- Cardiology
Background:
- Maternal propranolol (PRO) use is linked to fetal and neonatal adverse effects.
- Understanding PRO's impact on cardiac development is crucial for prenatal care.
Purpose of the Study:
- To investigate the effects of maternal PRO treatment on the developing heart in rat pups.
- To assess dose-dependent impacts on fetal growth and cardiac parameters.
Main Methods:
- Pregnant rats received subcutaneous PRO (25 or 50 mg/kg/day) from gestation days 8-20.
- Pup body weight, heart weight, protein, DNA, and ornithine decarboxylase (ODC) activity were measured postnatally.
Main Results:
- Maternal PRO treatment dose-dependently reduced pup body weight and heart weight at all tested ages.
- Decreased heart weight correlated with reduced heart protein, suggesting smaller cell size, not fewer cells.
- Basal and stimulated ODC activity remained unaffected, indicating intact sympathetic pathways and ODC response systems.
Conclusions:
- Prenatal PRO exposure leads to reduced fetal growth and cardiac development, primarily affecting cell size.
- Adverse effects may be linked to generalized maternal toxicity, evidenced by reduced maternal weight gain.
- Monitoring maternal weight gain during high-dose PRO therapy can help predict potential adverse fetal outcomes.
Abstract:
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.