oxymorphone and Hemorrhage

We tested the hypothesis that the pressor effect of naloxone during acute hemorrhagic hypotension is mediated in part at peripheral sites. Experiments were performed in conscious, chronically prepared rabbits. First, we compared the hemodynamic response to peripheral injections of naloxone and naloxone methobromide during acute hemorrhagic hypotension. Naloxone methobromide, which does not enter the central nervous system, produced a lesser pressor effect than naloxone. Second, we looked for peripheral effects of naloxone after close-arterial injection into the hindquarter vasculature. Unlike i.v. injections, close-arterial injection of naloxone did not produce any significant hemodynamic changes during hemorrhagic hypotension. Finally, we compared the capacities of naloxone and naloxone methobromide to block the peripherally mediated cardiovascular response to i.v. methionine-enkephalin in nonhemorrhaged animals. The potency of the two compounds, in terms of their blockade of this peripherally mediated response, was similar. The results of the present study do not support a predominant peripheral role for naloxone during acute hemorrhagic hypotension in conscious rabbits.

Topics: Animals; Blood Pressure; Endorphins; Enkephalin, Methionine; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Oxymorphone; Rabbits; Vascular Resistance

In the present study, the role of the endogenous opioid peptide systems in the regulation of blood pressure during standardized, stepwise hemorrhagic hypotension was investigated in anesthetized rats. Central as well as peripheral administration of naloxone resulted in an increase in the bleeding volumes required to reduce blood pressure. Bleeding volumes also increased after the peripheral injection of naloxone methobromide, an analog of naloxone that does not readily cross the blood-brain barrier. Following central administration of antisera against beta- and alpha-endorphin and dynorphin A(1-13), the amount of blood that had to be withdrawn to induce hypotension was elevated. In rats treated with an antiserum against [Met5] enkephalin or gamma-endorphin, bleeding volumes did not differ from those of rats treated with control serum. These data indicate that activation of central and possibly also of peripheral opiate receptors plays a role in the control of blood pressure during blood loss. Dynorphin A(1-13), beta- and alpha-endorphin, or closely related peptides might be the endogenous ligands for the receptors that are blocked by naloxone.

Topics: alpha-Endorphin; Animals; beta-Endorphin; Blood Pressure; Dynorphins; Endorphins; Enkephalin, Methionine; gamma-Endorphin; Hemorrhage; Hypotension; Immunization, Passive; Male; Naloxone; Oxymorphone; Peptide Fragments; Rats; Rats, Inbred Strains

The present study investigated the question of whether peripheral or central opiate receptors are activated during controlled haemorrhagic hypotension. In anaesthetized Wistar rats, blood pressure was reduced by steps, by bleeding, to 80, 60 and 40 mmHg. Subcutaneous administration of 1 mg/kg of naloxone and of methyl naloxone-Br, an analogue of naloxone, which does not readily cross the blood-brain barrier, significantly elevated the bleeding volume at the 40-mmHg blood pressure level. A dose of 10 mg/kg of methyl naloxone-Br had no effect on the bleeding volume. We therefore conclude that during haemorrhage, endogenous opioid peptides activate both central and peripheral opiate receptors, thereby exerting a hypotensive influence.

Topics: Animals; Central Nervous System; Hemorrhage; Hypotension; Male; Naloxone; Oxymorphone; Peripheral Nerves; Rats; Rats, Inbred Strains; Receptors, Opioid