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The aim of the present work was to investigate whether prostaglandins (PGs) are synthetized and released from isolated blood-perfused rat and cat lungs secondary to vasoconstriction induced by alveolar hypoxia. The lungs were perfused with autologous blood with constant volume inflow via the pulmonary artery in a recirculating system. They were ventilated with constant volume positive pressure, and acute alveolar hypoxia was induced by ventilation with a gas containing 2% O2. A superfusion bioassay technique was used to measure PG-like activity in the perfusate from the lungs, the blood being re-oxygenated before reaching the assay tissues. The oxygenator prevented the perfusate hypoxia induced by ventilation hypoxia to affect the bioassay tissues. The assay tissues were rat stomach strip, rat colon and chick rectum. They were sensitive to calibrating doses of 0.5--1 ng/ml PGE2 and 1--2 ng/ml PGF2alpha. In another series of experiments PGs of the F-series were measured in lung tissue from normoxic and hypoxic lungs with radioimmunoassay technique. No increase in PG-like activity could be detected in the venous effluent by means of bioassay during hypoxia, nor was the lung tissue content of immunoactive PGF increased by hypoxia. The present findings indicate that alveolar hypoxia does not stimulate PG-synthesis in lungs, refuting that PGs are important mediators of the pulmonary vasoconstrictor response to alveolar hypoxia. It is concluded that PGs play no significant role in producing the pressor response to alveolar hypoxia.

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.

We have compared the pulmonary vascular responses to a standardized hypoxic vasoconstrictor stimulus (FIO2 = 0.02) obtained during 1) constant volume inflow, with pulmonary arterial pressure as the dependent variable, and 2) constant inflow pressure, with flow as the dependent variable. Isolated rat lungs were perfused at different baseline transvascular pressures. The experimental arrangement allowed changes between the two types of perfusion. Hypoxia at constant pressure perfusion gave a higher percentage rise in pulmonary vascular resistance (PVR) at all pressure levels. This advantage was however, more than offset by the finding that a) vascular closure (total or partial) often occurred, particularly below arterial pressure of 3 kPa, making detection of graded responses impossible, and b) the control situation was rarely regained. Responses obtained during constant flow were less reduced by elevations in baseline transvascular pressure, and the control situtaion was rapidly and completely regained. The observation that hypoxic vascular closure may occur in the pulmonary vascular bed supports the hypothesis that high altitude edema is caused by precapillary occlusion of a major part of the vascular bed, thereby subjecting still perfused regions to very high pressure and flow.