Open AccessBaroreflex-Mediated Bradycardia Is Blunted by Intravenous μ- But Not κ-Opioid Agonists
Author(s) -
Abimbola T. Omoniyi,
Dunli Wu,
Yi Soong,
Hazel H. Szeto
Publication year - 1998
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199806000-00021
Subject(s) - damgo , bradycardia , baroreflex , reflex bradycardia , heart rate , agonist , tachycardia , opioid , medicine , endocrinology , blood pressure , anesthesia , phenylephrine , baroreceptor , propranolol , opioid receptor , receptor
To assess the cardiovascular effects of systemically administered opioid agonists, changes in blood pressure and heart rate were observed after 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-Ala2, N-Me-Phe4, Gly5-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 resulted in an immediate increase in blood pressure. The pressor response to U50,488H was accompanied by an increase in heart rate. In contrast, there was no accompanying change in heart rate in response to DAMGO. We hypothesized that the lack of a reflex bradycardia to the pressor responses of both the mu- and kappa-opioid-receptor agonists was due to a blunting of baroreflex-mediated bradycardia. The reflex bradycardia to norepinephrine (0.6 microg/kg/min) was significantly reduced in the presence of DAMGO but not U50,488H. In view of the lack of effect of U50,488H 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 elicited by U50,488H. These data suggest that the lack of a reflex bradycardia to the pressor response of DAMGO is due to a blunting of baroreflex-mediated bradycardia. In contrast, the increase in heart rate caused by U50,488H is mediated by sympathetic activation of the heart.