Pressor effect of nalbuphine in hemorrhagic shock is dependent on the sympathoadrenal system.
Nalbuphine, an analgesic with opiate agonist and antagonist properties, increases heart rate, mean arterial pressure (MAP), and cardiac function following a moderate hemorrhage in the rat. The interaction between opiate receptors and the sympathoadrenal system was examined in control, beta receptor-blocked, and adrenal-demedullated animals. MAP and heart rate were measured continuously in chronically instrumented conscious animals. Hemorrhage decreased MAP in the control group by 50%, and nalbuphine (1 mg/kg) returned this to prehemorrhage values within 5 min. MAP remained significantly greater in the nalbuphine-treated animals for 120 min. Heart rate fell with hemorrhage and increased above prehemorrhage values in the nalbuphine-treated animals. The pressor response to nalbuphine was abolished in both beta-blocked and adrenal-demedullated animals. Plasma catecholamines were not significantly elevated in the nalbuphine-treated as compared to control animals, which suggests that nalbuphine effects do not result from an enhancement of central mediated sympathoadrenal discharge. The opiate receptor antagonist naloxone, in a concentration that was not by itself effective in alleviating the hypotensive effects of hemorrhage, prevented the pressor response with nalbuphine. These results suggest that nalbuphine's beneficial effects in hemorrhagic shock depend on an intact sympathoadrenal system and on an interaction with opiate receptor sites, possibly in the heart.
Muldoon
S M
SM
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
McKenzie
J E
JE
Collins
F J
FJ
D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009266:Nalbuphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D011217:Practolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D009019:Morphinans; D011957:Receptors, Opioid; D009270:Naloxone; D009266:Nalbuphine; D011217:Practolol; D009638:Norepinephrine; D004837:Epinephrine