Nonopiate effect of naloxone on cardiac muscle contractility

To test the hypothesis that naloxone exerts a direct positive inotropic effect on the cardiac muscle, we employed two in vitro models. In one set of experiments we demonstrated that injection of 1 mg naloxone into an isolated perfused rat heart produced a significant increase in the amplitude of contraction. In another set of experiments we exposed an isolated and spontaneously contracting rat right atrium in a tissue bath to naloxone, and demonstrated that the amplitude of contraction increased significantly within a few minutes of naloxone administration. We showed that this effect of naloxone was not related to opiate receptors, since a similar effect was obtained with d-naloxone (the stereoisomer that is inactive as an opiate antagonist) and it was not affected by pretreatment with morphine. We also demonstrated that addition of alpha- and beta-adrenergic antagonists phentolamine and propranolol, in doses that effectively block alpha- and beta-adrenergic agonists, did not have any effect on naloxone's inotropic action. We validated our results in two electrically driven strips of human atrial myocardium in the tissue bath. A positive inotropic response to naloxone, measured as an increase of 80 and 50% in the amplitude of contraction, was noted. We postulate that naloxone's previously described cardiovascular pressor effect in states of shock may not only be related to reversal of the effects of endorphins but also to its direct inotropic action.