The pulmonary vasoconstrictor response to hypoxia. The hypoxia-sensitive site studied with a volatile inhibitor.

Recent investigations have revealed that a number of inhalation anesthetics, including halothane, inhibit the pulmonary vasoconstrictor response to hypoxia without affecting other vasoconstrictor stimuli. Various injectable anesthetics do not show this effect. This discrepancy could be due either to different pharmacological properties or to the different routes of administration. There is no general agreement on whether the response to hypoxia is elicited mainly by airway hypoxia or by blood hypoxemia, i.e. where within the lungs hypoxia acts. This work is an attempt to localize the hypoxia-sensitive site employing halothane. We have studied the reduction of standardized vasoconstrictor responses to hypoxia during administration of halothane via: (1) the airways, (2) the pulmonary artery and (3) the pulmonary veins (backward perfusion). Our experimental model has been two pairs of series-perfused hyperventilated isolated rat lungs. An equimolar concentration of halothane most effectively inhibits the response when presented to the alveoli, less when presented to the arterial- and least when presented to the venous segments of the pulmonary vasculature. We suggest that the response to hypoxia is inhibited by halothane at some extravascular site on the arterial side of the pulmonary vasculature, functionally closer to the alveoli than to the responding vessels. A model which combines all the data into an unifying concept has been presented.