Brain Research, 518 (1990) 143-148 Elsevier

143

BRES 15525

Changes in catecholamine metabolism in the rostral ventrolateral medulla following halothane and nitroprusside-induced hypotension: an in vivo electrochemical study Brian Milne, Luc Quintin and Jean-Yves Gillon Departments of Anesthesia and Pharmacology and Toxicology, Queen's University, Kingston, Ont. (Canada), Neuropharrnacologie Mol#culaire, Facult~ de M~decine Alexis Carrel, and Laboratoire de Physiologie de l'Environnement, Facult~ de M~decine Grange-Blanche, Lyon (France) (Accepted 14 November 1989) Key words: Adrenaline; Catecholamine; Circulation; Halothane; In vivo voltammetry; Noradrenalin; Nitroprusside; Rostral ventrolateral medulla

The objective was to observe changes in rostral ventrolateral medulla (RVLM) catecholamine metabolism using in vivo voltammetry following induced hypotension with halothane or nitroprusside (SNP). Rats anesthetized (halothane, metocurine) and ventilated were stereotaxically implanted with carbon microelectrodes in the RVLM. The catechoi oxidation current (CA.OC, % baseline) was used as an index of RVLM catecholaminergic metabolism. Groups of rats (n = 5) were given (A) halothane 0.75% for 60 min; (B) halothane 2.75% plus phenylephrine infusion to maintain mean arterial pressure (MAP) for 30 min, then haiothane 0.75% for 30 min; (C) halothane (2.5-3.0%) for 30 min (MAP 60 + 5 mmHg) then halothane 0.75% for 30 min; (D) halothane 0.75% and sodium nitroprusside (SNP) for 30 min (MAP 60 + 5 mmHg), then halothane 0.75% for 30 rain. Halothane 0.75% produced no significant change in CA.OC or MAP (A), while halothane 2.5-3.0% produced a significant decrease in MAP and a symmetrical significant increase in CA-OC (ANOVA, P < 0.5). This increase peaked at 30 min (180 + 28%) and reached 110 + 9% baseline at 60 min. The halothane and phenylephrine combination produced no significant change in CA.OC or MAP during the 30 min exposure (B). SNP (D) produced a significant increase in CA-OC (peak 48 min, 224 + 35%) which remained elevated at 60 min (198 + 32%). Thus, the induced hypotension produced activation of RVLM catecholaminergic neurons. SNP induced a prolonged significant increase in RVLM catecholamine metabolism which may relate to rebound hypertension following use of this drug.

INTRODUCTION In contrast to the caudal ventrolateral medulla involved in the baroreflex-mediated control of vasopressin secretion 2, the rostral ventrolateral medulla (RVLM) is involved in the generation of sympathetic tone 3,8'9,16,18. This structure is the final integrative structure of the efferent limb of the baroreflex 9'16. It contains both non-adrenergic neurons and adrenergic C 1 neurons which project to the intermediolateral cell column of the spinal cord. Thus, these neurons are likely involved in the control of sympathetic preganglionic cell bodies and of the circulatory system. However, the precise function of these adrenergic neurons within this system remains unsettled 9, partly because of the lack of a biochemically specific technique for their in vivo study in response to circulatory challenge. Indeed, several arguments suggest a lack of direct involvement of these adrenergic cell bodies within the baroreflex pathway itself 9. Thus, these adrenergic neurons may play a role not as a controller of

the baroreflex but only to modify somehow the functioning of non-adrenergic neurons which appear to act themselves as a central sympathetic generator 18. Direct proof of a dynamic and biochemically specific involvement of these C 1 adrenergic neurons during circulatory challenges is lacking. In this regard, in vivo voltammetry allows a quasi continuous, biochemically specific, monitoring of catecholamine metabolism in brain stem structures during circulatory challenges 4,13,14. Therefore, to assess whether metabolism of catecholamines in the R V L M is activated when the baroreflex is engaged, this study observes the response of catecholamine metabolism, taken as an indirect index of the activity of adrenergic C 1 cell bodies, to induced hypotension. Since induced hypotension is commonly used during clinical anesthesia using halothane or sodium nitroprusside (SNP) re'H, these two agents were employed to assess whether they would induce different patterns of catecholamine metabolism in the R V L M .

Correspondence: B. Milne, Department of Anaesthesia, Kingston General Hospital, 76 Stuart Street, Kingston, Ont., Canada K7L 2V7. 0006-8993/90/$03.50 t~) 1990 Elsevier Science Publishers B.V. (Biomedical Division)

144 halothane (1.5-2.0% during surgery, 0.75% during recording8) via a calibrated vaporizer and air/oxygen. A tracheotomy was done and mechanical ventilation (Harvard 50-1718) was established (f = 48 min+~), oxygen concentration 40-50%, to maintain an end tidal CO2 (Engstrom Eliza Duo modified with a neonatology kit) at 40 _+ 4 mmHg. Temperature was maintained at 37 + 0.5 °C rectal with a Harvard warming blanket. After induction of anesthesia, Ringer's lactate was continuously (Harvard syringe 568 816) infused at the rate of 5 ml.kg -].h -] via a femoral venous catheter. Arterial pressure

MATERIALS AND METHODS

General procedures Male Sprague-Dawley rats, 400-500 g, were housed (temperature 22 + 1 °C, light 7.00 h-19.00 h for at least 3 days prior to experimentation. Rat chow and water were given ad libitum. Anesthesia and monitoring of the animals have been detailed elsewhere~. Briefly, anesthesia was induced and maintained with

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