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The metabolic function of the lungs may be impaired in acute lung injuries. The present work examined the effect of toxic oxygen metabolites (TOM) on the pulmonary clearance of prostaglandin E2 (PGE2). Isolated rat lungs perfused with plasma were exposed to TOM, generated by xanthine oxidase (XO) and hypoxanthine (HX) in the perfusate. Inactivation of PGE2 was determined by superfusion bioassay technique. XO and HX (n = 6) reduced the inactivation of PGE2 from 78 +/- 4% (mean +/- SE) to 61 +/- 3%. This reduction was inhibited by the free radical scavengers superoxide dismutase and catalase, as well as by allopurinol, an inhibitor of XO. Neither hydrostatic lung edema nor perfusion per se decreased the inactivation of PGE2. Lungs pretreated with indomethacin still showed impaired PGE2 inactivation after exposure to XO and HX, indicating that a possible release of PGE2-like substances did not influence our findings. This study indicates that TOM may impair pulmonary metabolic function as shown by reduced inactivation of PGE2.

The pure and selective serotonin blocking agent ketanserin (5-HT2 receptor blocker) was used to evaluate a possible role for serotonin as a mediator of the pulmonary vasoconstrictor response to alveolar hypoxia. Isolated and ventilated lungs (FiO2 = 0.21) from rats were perfused at 310 degrees (K) with homologous blood at constant volume inflow, and pressor responses to standardized periods of ventilation hypoxia (FIO2 = 0.02) were recorded. Pressor responses to pulmonary arterial bolus-injections of serotonin were tested both before and after administration of ketanserin for comparison with the responses to hypoxia. We found that ketanserin in doses adequate to block the response to serotonin, had no effect on the pulmonary vasoconstrictor response to hypoxia.