Mechanism of growth retardation following chronic administration of beta-adrenoceptor antagonists to developing rats

A total of 112 3-week old Wistar rats were separated into eight groups: control groups I-IV (n = 62) and propranolol-treated groups V-VIII (n = 50). Propranolol hydrochloride (100 mg/kg) was present in the rats' drinking water until 26 weeks of age and growth rates of all groups were monitored daily until 53 days of age and thereafter every third day throughout the study. Chronic oral propranolol administration produced growth retardation (P less than 0.05) in both sexes that was reversible when treatment was discontinued. Organ weights were generally smaller in propranolol-treated rats; on the other hand, the ratio of most organ weights per 100 g of body weight was greater in propranolol-treated rats (especially females). The radio-immunological determination of plasma growth hormone showed increased concentrations of growth hormone in propranolol-treated rats (P less than 0.05), whereas hypothalamic somatostatin content was not significantly changed. The results showed that the retarded growth rate following chronic oral propranolol administration to growing rats was independent of changes in plasma growth hormone and hypothalamic somatostatin concentrations, and that retardation was entirely reversible when the beta-adrenoceptor antagonist was discontinued.