The effect of racemic, D-, or L-propranolol and practolol on the response to cold by the newborn rabbit.

Abstract

Summary: The newborn rabbit has been used as a model to investigate the effects of propranolol, the isomers of propranolol, and practolol on the response to cold exposure. Racemic propranolol(1 mg/kg) caused a significant drop in oxygen consumption and higher doses (2.25 and 5.0 mg/kg) abolished the rise caused by cold exposure (Table 1). This effect was not mimicked consistently by either the D or I isomer. Practolol had no significant effect at a 1.0 mg/kg dose but in the doses of 2.25 and 5.0 mg/kg completely blocked the cold-induced rise of oxygen consumption. Racemic propranolol caused an increased fall in colonic temperature which was significant when 2.25 mg/kg was used. Neither of the two propranolol isomers nor practolol had a significant effect on colonic temperature (Table 2). In contrast, both 2.25 and 5.0 mg/kg racemic propranolol and 2.25 mg/kg practolol caused a significantly greater drop in brown fat temperature than that caused by exposure to 25°. The isomers of propranolol did not affect brown fat temperature significantly (Table 3). The rise in serum free fatty acid (FFA) concentration induced by cold exposure was reduced or abolished by each drug in every dose used (Table 4). The rise in blood glucose due to cold was abolished by racemic propranolol and practolol in all doses used (Table 5). I-Propranolol significantly inhibited the rise in blood glucose from 60-90 min and caused a fall below the levels seen at 60 min. D-Propranolol had no effect on blood glucose levels. The results show that the fi blockers, propranolol and practolol, seriously compromise the response of the newborn rabbit to thermal stress.Speculation: Perinatal exposure to β blockers may compromise the metabolic response of the newborn infant to cold exposure. The mechanism of action of propranolol in this respect is nbt explained by the sum of the actions of its isomers.