INTRAVENOUSLY-INJECTED NALOXONE REVERSES THE DECREASE IN RENAL SYMPATHETIC-NERVE ACTIVITY SEEN DURING HYPOTENSIVE HEMORRHAGE IN CONSCIOUS RABBITS BY ACTING THROUGH CENTRAL MECHANISMS

The response of renal sympathetic nerve activity (RNA) to hemorrhage w as examined in chronically-instrumented conscious rabbits. Hemorrhage was induced at a rate of 5 ml/kg per min until the mean arterial press ure fell below 40 mmHg, The mean arterial pressure then remained at ar ound 80 mmHg until 10 ml/kg of hemorrhage (normotensive hemorrhage) be fore falling to below the pre-hemorrhagic control level (hypotensive h emorrhage). The RNA response showed a biphasic pattern, i.e., it incre ased during normotensive hemorrhage, then fell below the control level during hypotensive hemorrhage. To examine the mechanism involved in t his decrease in RNA, naloxone (7.5 mu mol/kg), an opioidergic receptor antagonist, was intravenously injected 1 min after the end of hemorrh age. Intravenous injection of naloxone caused an increase in mean arte rial pressure and RNA to the level seen during normotensive hemorrhage . These results indicate that the decrease in RNA induced by hypotensi ve hemorrhage is mediated by opioidergic receptors. To determine wheth er the effects of naloxone are mediated via central or peripheral opio idergic receptors, naloxone was replaced by an equimolar solution of m ethylnaloxone, a form unable to cross the blood-brain barrier. Neither the mean arterial pressure nor RNA was significantly altered by admin istration of methyl naloxone, These results suggest that the effects o f naloxone on both the RNA and the mean arterial pressure are mediated via central opioidergic receptors, i.e., the sympathoinhibition induc ed by hypotensive hemorrhage is mediated via the stimulation of centra l opioidergic receptors.