Opioids potentiate contractile response of rabbit myocardium to the beta adrenergic agonist isoproterenol.
Opioid agonists and antagonists have both been reported to augment myocardial contractile force in vitro. We reported that the strong opioid agonists morphine and levorphanol, the weak agonist dextrorphan (an optical isomer of levorphanol), and the opioid antagonist naloxone all potentiate the stimulatory effects of the beta-adrenergic agonist isoproterenol on isometric tension generated by isolated rabbit right ventricular myocardium. The EC50 of isoproterenol was found to be shifted leftward 2.7-, 5.4-, 5.3-, and 3.4-fold respectively (p less than 0.05 when compared with controls), when the opioids were added at a final concentration of 1 x 10(5) M. Lower concentrations of opioid or antagonist did not potentiate the effects of isoproterenol. The rank order potency for potentiation thus differs markedly from that of opioid analgesia. The observed potentiation is therefore not agonist specific and not stereospecific. Furthermore, the drugs alone at a range of concentration from 10(-8) to 10(-5) M had no effect on isometric tension generated. We conclude that opioid agonists and antagonists potentiate the response of ventricular myocardium to the effects of beta-adrenergic stimulation by a novel mechanism unrelated to the binding of these drugs to opioid receptors. The paradoxical augmentation of myocardial contractility by either class of agent under a variety of clinical and experimental conditions is thus explained by these findings. Either agent may interact with myocardial tissue to cause increased sensitivity to stimulation by circulating catecholamines.
Kindman
L A
LA
Department of Medicine, Stanford University Medical Center, California 94305-5246.
Kates
R E
RE
Ginsburg
R
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003917:Dextrorphan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D007981:Levorphanol / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011817:Rabbits; D011957:Receptors, Opioid / Q000502:physiology; D013268:Stimulation, Chemical; D016278:Ventricular Function, Right / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D009294:Narcotics; D011957:Receptors, Opioid; D003917:Dextrorphan; D007981:Levorphanol; D009270:Naloxone; D009020:Morphine; D006632:Histamine; D007545:Isoproterenol