THERMOREGULATORY RESPONSES TO BETA-ADRENERGIC AGONISTS AT LOW AMBIENT-TEMPERATURES IN THE RAT

Dose-response effects on heat production (HP) and dry heat loss (DHL) following injection with the non-selective (beta1/beta2) adrenergic agonist isoprenaline (ISO) and the atypical B3 agonist BRL 35135 (BRL) were established at an ambient temperature of 25-degrees-C in rats. Subsequently, the effects on HP and DHL of a maximal thermogenic dose of ISO (75 mug/kg) and a supramaximal dose of BRL (40 mug/kg) were tested at ambient temperatures of 5, 10 and 15-degrees-C. In terms of heat production, BRL was no different from saline at 5-degrees-C, but its thermogenic activity became increasingly evident as ambient temperature increased. For ISO, HP was lower than, or no different from, saline at 5 and 10-degrees-C, respectively, but DHL exceeded HP at both temperatures, and colonic temperature fell significantly; ISO and BRL responses were similar at 15-degrees-C. ISO was also capable of producing a decrease in HP at 10-degrees-C if the rats were shaven. Substitution for endogenous, sympathetically mediated thermogenesis would explain the attenuation of the BRL and ISO effects at cool ambient temperatures, whereas the hypothermic effects of ISO in the cold appeared to be due to an inappropriate increase in DHL, which was exacerbated at 5-degrees-C by a reduction in HP below saline values. The increase in DHL was consistent with beta2-mediated effects of ISO on peripheral blood flow, but the mechanism responsible for the reduction in HP in the cold is unknown, although reduced vascular thermogenesis has been offered as a putative explanation.