Halothane differentially decreases 5-hydroxytryptamine-induced contractions in normal and chronic hypoxic rat...

The mechanism of action of halothane is not fully understood in pulmonary circulation and especially in chronic hypertension models. As the 5-hydroxytryptamine (5-HT) pulmonary vasoconstrictor response increases in chronic hypoxic rat, halothane could differentially attenuate this vasoconstriction response on normoxic and chronic hypoxic rats. The effect of halothane on 5-HT-induced contractions on pulmonary arteries isolated from normoxic and chronic hypoxic rats was compared. Rings dissected from proximal pulmonary artery without endothelium were attached to a force transducer to record tone and placed in an organ chamber gassed either by air or air + halothane (1-5%). Contractions induced by (10(-4) M) 5-HT were used to test the effect of halothane on rings isolated from normoxic and chronic hypoxic rats. 5-Hydroxytryptamine-mediated contractions were more sensitive to external calcium in normoxic than chronic hypoxic rings. In calcium-free solution, with verapamil or cadmium the amplitude of remaining 5-HT-induced contractions were greater in chronic hypoxic rings. Halothane (1-5%) decreased 5-HT-mediated contractions in normoxic and chronic hypoxic rings. The effect occurred with no change of pD2 for 5-HT and was more pronounced in normoxic rings. The effect of halothane on both rings was abolished in the absence of external calcium or in the presence of verapamil. In the presence of cadmium, 5% halothane had no effect on normoxic rings but still decreased the remaining 5-HT contraction on chronic hypoxic rings. The findings suggested that halothane decreased sarcolemmal calcium entry in pulmonary artery rings by a cadmium-sensitive pathway in normoxic rats and by a cadmium-insensitive pathway in chronic hypoxic rats.