title: The opiate antagonist naloxone counteracts the inhibition of sympathetic nerve activity caused by halothane anesthesia in rats.
abstract: The study was undertaken to examine if endogenous opioid systems mediate the response of the sympathetic nervous system to halothane anesthesia. Steady state values of renal sympathetic nerve activity (rSNA), mean arterial pressure (MAP), and heart rate (HR) were continuously recorded in the conscious state and at three depths of halothane anesthesia (0.6%, 1.2%, and 2.4%) in rats. Halothane caused an inhibition of rSNA and hypotension and a decrease in HR at the three halothane concentrations. Repeated bolus doses of the opiate antagonist (-)naloxone given iv during 1.2% halothane anesthesia did not significantly increase any of the variables. However, pretreatment with (-)naloxone (2 or 15 mg.kg-1) induced an increase in rSNA at 0.6% halothane, and subsequently the rSNA inhibition was less pronounced at the two higher halothane concentrations compared with control. HR showed a similar pattern, whereas the hypotension was essentially unaffected. Pretreatment with the pharmacologically inactive compound (+)naloxone had no effect on the halothane-induced depression of rSNA. The ED50 halothane concentration concerning nociceptive aversive behavior was not significantly changed with (-)naloxone pretreatment (2 mg.kg-1). In order to determine if sympathoinhibitory bulbospinal serotonin pathways are activated during halothane anesthesia, rSNA, MAP, and HR were recorded in rats pretreated with the serotonin synthesis inhibitor parachlorophenylalanine (PCPA). However, PCPA pretreatment did not affect the rSNA response to halothane compared with control. These findings indicate that the halothane-induced inhibition of rSNA might partially result from a stereospecific activation of opioid receptors, whereas halothane analgesia does not seem to be mediated by opioid mechanisms.
authors.affiliation: Department of Physiology, Sahlgrens Hospital, University of Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Delle
authors.forename: S E
authors.initials: SE
authors.lastname: Ricksten
authors.forename: P
authors.initials: P
authors.lastname: Thorén
mesh_terms: D000769:Anesthesia, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006221:Halothane / Q000037:antagonists & inhibitors*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D009270:Naloxone; D006221:Halothane