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 was examined in chronically-instrumented conscious rabbits. Hemorrhage was induced at a rate of 5 ml/kg per min until the mean arterial pressure fell below 40 mmHg. The mean arterial pressure then remained at around 80 mmHg until 10 ml/kg of hemorrhage (normotensive hemorrhage) before falling to below the pre-hemorrhagic control level (hypotensive hemorrhage). The RNA response showed a biphasic pattern, i.e., it increased during normotensive hemorrhage, then fell below the control level during hypotensive hemorrhage. To examine the mechanism involved in this decrease in RNA, naloxone (7.5 mumol/kg), an opioidergic receptor antagonist, was intravenously injected 1 min after the end of hemorrhage. Intravenous injection of naloxone caused an increase in mean arterial pressure and RNA to the level seen during normotensive hemorrhage. These results indicate that the decrease in RNA induced by hypotensive hemorrhage is mediated by opioidergic receptors. To determine whether the effects of naloxone are mediated via central or peripheral opioidergic receptors, naloxone was replaced by an equimolar solution of methylnaloxone, a form unable to cross the blood-brain barrier. Neither the mean arterial pressure nor RNA was significantly altered by administration of methyl naloxone. These results suggest that the effects of naloxone on both the RNA and the mean arterial pressure are mediated via central opioidergic receptors, i.e., the sympathoinhibition induced by hypotensive hemorrhage is mediated via the stimulation of central opioidergic receptors.
Yamashita
Y
Y
Department of Physiology, Kagawa Medical School, Japan.
Nagamachi
K
K
Morita
H
H
Nishida
Y
Y
Tanaka
S
S
Maeta
H
H
Hosomi
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors
D009270:Naloxone