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.
Sirén
A L
AL
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Paakkari
P
P
Goldstein
D S
DS
Feuerstein
G
G
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000701:Analgesics, Opioid; D002395:Catecholamines; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C030058:dermorphin; D009270:Naloxone