Analysis of cardiovascular effects of morphine in the cat

In cats anaesthetized with chloralose, the effect of morphine on arterial blood pressure and heart rate was examined by injecting the drug through different routes. When injected into the cerebral ventricles, it acted on structures in the walls of the third ventricle and produced a naloxone resistant tachycardia through a sympathetic discharge to the heart. When injected into the cisterna magna or subcutaneously, it produced a naloxone sensitive long-lasting fall in blood pressure and bradycardia resulting from inhibition of sympathetic tone to blood vessels and heart; increased vagal tone played a minor role in the development of bradycardia. When injected intracisternally or subcutaneously, morphine acted near the obex at the dorsal surface of the medulla, because it produced the same circulatory effects but in much smaller doses when applied to this region on a piece of filter paper. Conversely, small doses of naloxone similarly applied abolished or prevented the circulatory effects of subcutaneous morphine. The action of morphine may be on the commissural nucleus of the tractus solitarius. Intravenous naloxone restored the circulatory effects of intracisternal and subcutaneous morphine and sometimes produced a pronounced overshoot, but without a preceding injection of morphine, naloxone had no effect on circulation. It is suggested that inhibition of sympathetic tone to the cardiovascular system by an action on structures near the obex is the mechanism by which morphine produces in man orthostatic hypotension and its beneficial effect in left ventricular failure.