title: Sympathetic activity in the rat: effects of anaesthesia on noradrenaline kinetics.
abstract: Noradrenaline (NA) kinetics represent an effective tool for evaluating the activity of the sympathetic system: thus plasma NA concentration, spillover rate (SOR) and metabolic clearance rate (MC) were measured in the rat. The dilution technique was adapted and validated: pithing that caused mechanical destruction of the spinal cord was shown to reduce drastically NA-SOR and plasma NA concentration with no effect on NA-MC. NA-SOR and plasma NA concentration were restored within their normal limits when 2.5 Hz electrical stimulation of the sympathetic roots was superimposed. Normal values of NA kinetics in non-anaesthetised normotensive 12-week-old rats are reported: NA-SOR=196.1+/-26.4 ng/kg/min, NA-MC=413.9+/-38.8 ml/kg/min and plasma NA=486+/-52 pg/ml. NA kinetic was investigated in response to anaesthesia, known to depress excitable tissues of the central nervous system and expected to depress the activity of the sympathetic system. When NA-SOR was significantly reduced during anaesthesia with either sodium pentobarbital or chloralose, plasma NA concentration was not changed because NA-MC was also reduced. Thus, plasma NA concentration can be a misleading marker of the sympathetic activity. The response of the sympathetic activity to four different anaesthetic agents is shown to be heterogeneous, ranging from inhibition to stimulation. Sodium pentobarbital anaesthesia was associated with a statistically significant reduction of both NA-SOR (105.6+/-14.1 ng/kg/min, P<0. 01) and NA-MC (239.3+/-18.7 ml/kg/min, P<0.001) while plasma NA was not changed (438+/-47 pg/ml). Chloralose reduced NA-SOR (101.6+/-20. 1 ng/kg/min, P<0.05) while ketamine did not (150.6+/-35.5 ng/kg/min, n.s.): both compounds reduced NA-MC (257.9+/-27.8 ml/kg/min, P<0.01 and 265.8+/-34.3 ml/kg/min, P<0.05, respectively). Diethyl ether was shown to increase both NA-SOR (472.2+/-111 ng/kg/min, P<0.05) and plasma NA concentration (1589+/-436 pg/ml, P<0.01), while NA-MC remained unchanged. Thus, any investigation of the activity of the sympathetic system in the anaesthetised rat has to take into account the specific effects related to the anaesthetic agent used.
authors.affiliation: Catecholamine Biology Research Laboratory, INSERM U-337 & Broussais Faculty of Medicine, 15 rue de l'Ecole de Médecine, 75270, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Maignan
authors.forename: W X
authors.initials: WX
authors.lastname: Dong
authors.forename: M
authors.initials: M
authors.lastname: Legrand
authors.forename: M
authors.initials: M
authors.lastname: Safar
authors.forename: J L
authors.initials: JL
authors.lastname: Cuche
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002698:Chloralose / Q000494:pharmacology; D004986:Ether / Q000494:pharmacology; D006339:Heart Rate; D007649:Ketamine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000759:Adjuvants, Anesthesia; D000778:Anesthetics, Dissociative; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D004986:Ether; D002698:Chloralose; D007649:Ketamine; D010424:Pentobarbital; D009638:Norepinephrine