Effects of reduced pulmonary flow and hypoxia on metabolism of serotonin by rat lungs perfused in situ.

Abstract

To investigate the extent to which reduced pulmonary flow may affect non-ventilatory functions of the lung, pulmonary artery pressures were altered systematically in an in vitro perfused lung preparation. Metabolic integrity of the tissue was assessed at two levels: disposition of exogenous serotonin (5-hydroxytryptamine; 5-HT) was monitored as a specific indicator of endothelial cell metabolism; and whole-tissue rates of protein synthesis and levels of ATP were evaluated as indices of general metabolic activity and energy availability. Rat lungs were perfused with recirculating cell-free buffer (37 degrees C) for 1 or 3 h at high (36) or low (3 ml.min-1.g-1) pulmonary flow; initial rates of 5-HT metabolism were measured over a subsequent 2-min interval of single-pass perfusion. Metabolism of 5-HT was inhibited and protein synthesis decreased 35% at low pulmonary flow. These changes did not appear to result directly from hypoxia, nor from the associated fall in tissue ATP. The effects of low flow were not reversed at high PO2, nor was 5-HT metabolism inhibited by restricted oxygen availability at high flow rates. After as long as 3 h exposure to a combination of low flow, ventilation (V = 0), and temperature (27 degrees C) and to the volatile anesthetic, halothane, inhibitory effects on both amine and protein metabolism were rapidly reversible. Reductions in the rate of 5-HT metabolism at reduced flow involved a decrease in the maximal velocity (Vmax: 8.0 to 2.2 nmol.min-1.g-1), without change in the apparent Km (2.6-3.2 microM) of the pathway for amine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)