Involvement of both adrenergic and cholinergic receptors in the cardiovascular effects of naloxone during hemorrhagic hypotension in the conscious rabbit.
Opiate receptor blockade with naloxone reverses the hypotension associated with severe hemorrhage in a variety of animal models. In the present study, we examined the mechanisms of naloxone's actions in conscious rabbits made hypotensive by hemorrhage. This was accomplished through pharmacological blockade of the efferent limbs of the sympathetic or parasympathetic nervous systems prior to naloxone injection. In addition, we examined the effects of naltrexone in the same model. Naloxone treatment in hypotensive-hypovolemic, conscious rabbits results in an increase in mean arterial blood pressure (BP) and a decrease in heart rate (HR). The bradycardia appears to be due to a reduction in beta-adrenergic and an increase in muscarinic-cholinergic activity. The pressor effect is apparently due to increased alpha-adrenergic receptor activation, and is accompanied by an increase in cardiac output, stroke volume, and total peripheral resistance. Naltrexone did not significantly affect BP but it did reduce HR. The results from the present study suggest that naloxone's effects are mediated by an integrated response of the sympathetic and parasympathetic nervous systems. The actions of naloxone may be mediated through antagonism of endogenous opiates.
D000320:Adrenergic Fibers / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004525:Efferent Pathways / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000150:complications*; D007022:Hypotension / Q000188:drug therapy*; D008297:Male; D009270:Naloxone / Q000627:therapeutic use*; D009271:Naltrexone / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects
D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; D001285:Atropine; D011433:Propranolol; D010646:Phentolamine