Effects of prolonged administration of a β-agonist drug, ritodrine, on cardiovascular, metabolic and endocrine responses to adrenaline in growing ram lambs

Abstract

SUMMARYFive Suffolk crossbred ram lambs were administered ritodrine, a β2-agonist drug, by continuous intravenous infusion at 0·5 μg/kg per min for 9 days to determine effects of prolonged β-agonist infusion on metabolism and on the responsiveness of the animals to short-term infusions of adrenaline. Consistent with other investigations, this study showed that initially the drug caused rapid increases in heart rate and plasma concentrations of free fatty acids (FFA), lactate and insulin, but decreased plasma growth hormone. There was no effect on plasma glucose or pancreatic glucagon concentrations. After 24 h of ritodrine infusion, these effects were attenuated as tachyphylaxis to the drug developed. On days 2–9 of the infusion, heart rate remained significantly higher than preinfusion values, but plasma glucose concentration was significantly lower than before infusion. Despite the rapid disappearance of these ‘side-effects’ of the drug and the apparent normality of most metabolic parameters, short-term infusion of adrenaline (50 ng/kg per min for 60 min then 500 ng/kg per min for a further 60 min) after 9 days of ritodrine infusion showed that the responses of lactate, FFA and heart rate to adrenaline were significantly attenuated in comparison with the responses determined before β-agonist infusion. This result, together with similar earlier observations on fetal lambs, implies that selective attenuation of β-receptor mediated cardiovascular, metabolic and endocrine responses to the endogenous catecholamines could play an important role in determining how β-agonist drugs act to modify carcass development.