Involvement of sympathetic activation and brown adipose tissue in calcitonin gene-related peptide-induced heat production in the rat

We previously reported that microinjection of calcitonin gene-related peptide (CGRP; 1.6-8.0 pmol, 0.2-1.0 mu l) into the ventromedial hypothalamus (VMH) increased oxygen consumption (VO2), heart rate (HR), colonic temperature (T-co), and temperature of interscapular brown adipose tissue (T-IBAT). In the present study, we investigated whether thr autonomic nervous system is involved in the CGRP-induced heat production in urethane-anesthetized rats. Intraperitoneal administration of the ganglion blocker hexamethonium (20 mg/kg) or the beta-adrenergic antagonist propranolol (5 mg/kg) suppressed the CGRP-induced increases in VO2. HR, T-co, and T-IBAT. Pretreatment with the cr-adrenergic antagonist phentolamine (5 mg/kg) partly attenuated the heat production response but did not affect the tachycardiac response. Bilateral sectioning of the nerves supplying the IBAT attenuated the CGRP-induced increase in T-IBAT but not significantly that in VO2 or T-co. In rats with adrenal demedullation, the effects of CGRP were similar to those in intact rats. These results suggest that the CGRP-induced heat production is mediated by the sympathetic nervous system and, at least in part, by the BAT through the alpha- and beta-adrenoceptors. (C) 1999 Elsevier Science B.V. All rights reserved.