Comparison of cardiovascular effects of mu- and delta-opioid receptor antagonists in dogs with congestive heart failure.
We have shown previously that right heart failure (RHF) in dogs is associated with activated endogenous opiate systems, and that administration of the opioid receptor antagonist, naloxone, increases arterial pressure, cardiac contractile function and organ blood flows. To study whether the cardiovascular effects of naloxone are mediated via the mu- or delta-opioid receptors, we administered ICI-154,129, a delta-receptor antagonist, and naloxonazine, a mu-receptor antagonist, to 10 conscious dogs with RHF on 2 separate days. Like naloxone, ICI-154,129 increased mean aortic pressure, cardiac output, peak positive first derivative of left ventricular pressure, and blood flows to the myocardium, kidneys, splanchnic beds, and skeletal muscle. These changes were associated with increases in plasma epinephrine and norepinephrine. In contrast, naloxonazine had no effects on systemic hemodynamics, regional blood flow distribution, and plasma catecholamines in RHF. These findings suggest that the increased endogenous opioids during heart failure act on the delta-opioid receptors to decrease myocardial mechanical performance and alter regional blood flow distribution. Opioid receptor-blocking agents may exert beneficial cardiovascular effects in heart failure.
Imai
N
N
Department of Medicine, University of Rochester Medical Center, New York 14642.
Kashiki
M
M
Woolf
P D
PD
Liang
C S
CS
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow / Q000187:drug effects; D016278:Ventricular Function, Right
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004743:Enkephalin, Leucine; C034643:naloxonazine; C036405:ICI 154129