Effect of volatile anesthetics on endogenous tryptophan, 5-hydroxytryptophan and 5-hydroxytryptamine in rat lung.

Volatile anesthetics inhibit the pulmonary inactivation of 5-hydroxytryptamine (5-HT) possibly via an effect on endogenous lung 5-HT. The consequent higher systemic arterial 5-HT concentrations may predispose the heart to dysrhythmias. The direct effect of the anesthetics on endogenous 5-HT, its metabolites, and precursors in the isolated ventilated perfused rat lung was determined by high-pressure liquid chromatography. Halothane (0.45, 1.4, and 2.3 minimum alveolar concentration (MAC] and 35% nitrous oxide (N2O) increased lung 5-HT (11, 70, 94, and 54% respectively). The effect of 0.45 MAC halothane and 35% N2O on 5-HT was synergistic. Isoflurane (2.9 MAC) had no effect on lung 5-HT. The lung concentration of tryptophan (TRP) was increased 51% by 2.9 MAC isoflurane, but the rate of efflux of TRP from the lung was unchanged. There was no effect of the anesthetics on 5-hydroxytryptophan (5-HTP). The ratio of 5-HT:5-HTP was significantly increased by 2.3 MAC halothane and 0.5 MAC halothane +35% N2O. The 5-HTP:TRP ratio was unchanged. The metabolite of 5-HT, 5-hydroxyindole acetic acid (5-HIAA), was not always detected. The results suggest that the increase in lung 5-HT by halothane reflects an increase in 5-HTP decarboxylase activity and that halothane and isoflurane exert selective effects on lung 5-HT synthesis. The results do not support the hypothesis that lung 5-HT controls the inactivation of 5-HT in the pulmonary circulation.