DOSE-DEPENDENT INCREASES IN THE RENAL SYMPATHETIC-NERVE ACTIVITY DURING RAPID INCREASE IN ISOFLURANE CONCENTRATION IN INTACT, LOWER AIRWAY-DEAFFERENTED, AND BARORECEPTOR-DEAFFERENTED RABBITS

Background: The inhalation of high concentrations of isoflurane has be en reported to increase the heart rate and the concentration of serum catecholamines, Although the precise mechanisms for the sympathetic ac tivation of isoflurane have yet to be clearly elucidated, they are con sidered to possibly originate from the stimulation of airway sensory a fferents, the baroreceptor reflex, or the direct stimulation of the ce ntral nervous system. To determine how these three mechanisms contribu te to sympathetic augmentation, the effects of lower airway deafferent ation and baroreceptor deafferentation on the isoflurane-induced chang es in the renal sympathetic nerve activity (RSNA) in tracheally intuba ted rabbits were examined. Methods: Twenty rabbits were given basal an esthesia. After tracheotomy and during mechanical ventilation, the cha nges in the heart rate, mean arterial pressure, and RSNA La response t o random exposures to 1%, 2%, 3%, and 4% isoflurane were examined. The animals were assigned to one of three groups; 1, the intact group (n = 6); 2, the baroreceptor-deafferented group (n = 9), in which the sin oaortic plus vagal nerves were cut; and 3, the lower airway-deafferent ed group (n = 5), which underwent a bilateral vagotomy, The exposure t o isoflurane was for 10 min in group 1 and 5 min in groups 2 and 3, At least 1 h was allowed for the recovery interval between exposures to isoflurane. Results: The inhalation of isoflurane caused dose-dependen t increases in RSNA in all three groups. RSNA during high concentratio ns of isoflurane began to increase at 1 min, reaching the maximum at 4 or 5 min in group 1 (2.8- and 3.8-fold at 3% and 4% isoflurane, respe ctively) and group 3 (2.8- and 4.5-fold at 3% and 4% isoflurane, respe ctively), but it reached the peak at 2 or 3 min in group 2 (1.7- and 2 .4-fold at 3% and 4% isoflurane, respectively) after the initiation of inhalation, in association with early slight increases followed by de creases of mean arterial pressure in groups 1 and 2 but only gradual d ecreases of mean arterial pressure in group 3. The increases in RSNA i n group 3 were similar to group 1, however, those in group 2 were sign ificantly attenuated compared with group 1. Conclusions: The inhalatio n of isoflurane caused an increase of RSNA in intact, baroreceptor-dea fferented, and lower airway-deafferented rabbits. The extent of the in creases in RSNA was greater in intact and lower airway-deafferented ra bbits than in baroreceptor-deafferented rabbits. Therefore, it is sugg ested that isoflurane may increase the efferent sympathetic nerve acti vity via the direct stimulation of the central nervous system and via the arterial baroreceptor reflex reflecting the reduction in arterial blood pressure, The stimulation of the vagally innervated airway may n ot contribute to the increase in the sympathetic nerve activity by iso flurane.