POTENTIATION OF THERMOREGULATORY RESPONSES TO ISOPROTERENOL BY BETA-ADRENERGIC ANTAGONISTS

The thermoregulatory effects of isothermogenic doses of isoproterenol (Iso) and a novel beta-agonist (BRL 35135) were tested in rats at 22-degrees-C and in rats trained to bar press for radiant heat at -8-degrees-C. BRL 35135 produced hyperthermia at 22-degrees-C and reduced operant responding for heat at -8-degrees-C, whereas Iso reduced body temperature and increased operant responding. In both situations, the negative effects of Iso on thermal balance were abolished by propranolol at doses that did not inhibit heat production. In anesthetized rats, propranolol potentiated the Iso-induced rise in brown adipose tissue and colonic temperature. The potentiation was more marked with the beta2-selective antagonist ICI 118,551, whereas treatment with the beta1-selective antagonist atenolol resulted in a profound Iso-induced reduction in temperature. The two selective antagonists also produced divergent responses in operant behavior in Iso-treated rats at -8-degrees-C. These experiments demonstrate the extent to which responses to a nonselective agonist can be manipulated using appropriately low doses of selective antagonists and indicate that the effects of Iso on thermal balance are due to its beta2 activity.