Morphine sulfate depression of cardiac function is attenuated by opiate receptor antagonism with naloxone

In previous work, morphine sulfate was shown to decrease heart rate (HR) and cardiac output (CO) in a dose-related fashion. It was hypothesized that this effect was mediated by opiate receptors located in the myocardium. The present study evaluated the effect of opiate receptor antagonism with naloxone using a modified Langendorff rat heart perfusion apparatus. Sixty-five rat hearts were excised and perfused with Krebs-Henseleit buffer (KHB) solution, to which morphine sulfate and naloxone (NAL) were added in different concentrations. In the initial studies, NAL (10(-5) M) was added to the perfusate prior to the incremental additions of morphine. This resulted in no antagonism of the previously described opiate agonist effects. Norepinephrine (NE; 10(-9) M) was then added to the perfusate prior to the NAL or morphine. The NE did not affect the dose-related decrease in HR and CO when morphine was added but did permit the attenuation of the morphine effect by the addition of increasing concentrations of NAL up to 10(-5) M. These results suggest that the agonist effect can be attenuated by opiate receptor antagonism with NAL; the data also suggest a possible interrelationship between opiate and catecholamine receptor activity in the myocardium.