Mechanisms of central hemodynamic and sympathetic regulation by mu opioid receptors: effects of dermorphin in the conscious rat.

The effects of i.c.v. administered dermorphin, a highly selective mu-opioid agonist, on cardiac function and renal, mesenteric and hindquarter blood flow were studied in conscious rats. Core temperature, blood gases, arterial plasma levels of norepinephrine, epinephrine, dopamine, 3,4-dihydroxyphenylalanine and dihydroxyphenylacetic acid (DOPAC) also were examined. Cardiac output was measured using a thermodilution technique and regional blood flows using directional pulsed Doppler velocimetry. Dermorphin, at doses of 0.1-100 nmol/kg, increased blood pressure and hindquarter blood flow, renal and mesenteric resistance, and core temperature. Higher doses (1-5 mumol/kg) caused respiratory depression, acidosis, and shock despite profound sympatho-adrenomedullary stimulation. Circulating levels of catecholamines were significantly increased at the dermorphin doses of 0.1-100 nmol/kg. At the 100 nmol/kg dose, plasma levels of epinephrine, norepinephrine, the dopamine metabolite dihydroxyphenylacetic acid and the catecholamine precursor 3,4-dihydroxyphenylalanine were increased by 2-15-fold. The data indicate that mu opioid receptor stimulation exerts potent effects on cardiorespiratory functions, activates the sympathoadrenomedullary system and produces a pattern of blood flow changes consistent with the stress-induced "defense" response (skeletal muscle vasodilation and splanchnic vasoconstriction). Excessive mu opioid receptor stimulation leads to shock due to respiratory and hemodynamic collapse.