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

The mechanism of action of halothane is not fully understood in pulmonary c irculation and especially in chronic hypertension models. As the 5-hydroxyt ryptamine (5-HT) pulmonary vasoconstrictor response increases in chronic hy poxic rat, halothane could differentially attenuate this vasoconstriction r esponse on normoxic and chronic hypoxic rats. The effect of halothane on 5- HT-induced contractions on pulmonary arteries isolated from normoxic and ch ronic hypoxic rats was compared. Rings dissected from proximal pulmonary ar tery 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 o f halothane on rings isolated from normoxic and chronic hypoxic rats. 5-Hyd roxytryptamine-mediated contractions were more sensitive to external calciu m in normoxic than chronic hypoxic rings, In calcium-free solution, with ve rapamil or cadmium the amplitude of remaining 5-HT-induced contractions wer e greater in chronic hypoxic rings, Halothane (1-5%) decreased 5-HT-mediate d contractions in normoxic and chronic hypoxic rings. The effect occurred w ith no change of pD(2) for 5-HT and was more pronounced in normoxic rings. The effect of halothane or both rings was abolished in the absence of exter nal calcium or in the presence of verapamil, In the presence of cadmium, 5% halothane had no effect on normoxic rings but still decreased the remainin g 5-HT contraction on chronic hypoxic rings. The findings suggested that ha lothane decreased sarcolemmal calcium entry in pulmonary artery rings by a cadmium-sensitive pathway in normoxic rats and by a cadmium-insensitive pat hway In chronic hypoxic rats.