Peripheral opioidergic mechanisms do not mediate naloxone's pressor effect in the conscious rabbit

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.