BAROREFLEX-MEDIATED BRADYCARDIA IS BLUNTED BY INTRAVENOUS MU-OPIOID BUT NOT KAPPA-OPIOID AGONISTS

To assess the cardiovascular effects of systemically administered opio id agonists, changes in blood pressure and heart rate were observed af ter intravenous (i.v.) administration of U50,488H (trans-3,4-dichloro- N-[2-(1-pyrrolidinyl) cyclohexyl]benzeneacetamide), a selective kappa- opioid receptor agonist, and DAMGO (D-Ala(2), N-Me-Phe(4), Gly(5)-ol), a selective mu-opioid-receptor agonist. Intravenous administration of U50,488H (1.2 mg/kg) and DAMGO (0.3 mg/kg) to the awake sheep resulte d in an immediate increase in blood pressure. The presser response to U50,488H was accompanied by an increase in heart rate. In contrast, th ere was no accompanying change in heart rate in response to DAMGO. We hypothesized that the lack of a reflex bradycardia to the presser resp onses of both the mu- and kappa-opioid-receptor agonists was due to a blunting of baroreflex-mediated bradycardia. The reflex bradycardia to nonpinephrine (0.6 mu g/kg/min) was significantly reduced in the pres ence of DAMGO but not U50,488H. In view of the lack of effect of U50,4 88H on the baroreflex, we further hypothesized that the tachycardia it elicited was due to an increase in sympathetic activity. Pretreatment with propranolol (0.1 mg/kg) completely blocked the tachycardia elici ted by U50, 488H. These data suggest that the lack of a reflex bradyca rdia to the pressor response of DAMGO is due to a blunting of barorefl ex-mediated bradycardia. In contrast, the increase in heart rate cause d by U50,488H is mediated by sympathetic activation of the heart.