Xanthine Oxidase-Induced Lung Injury Inhibits Removal of 5-Hydroxytryptamine from the Pulmonary Circulation

: We were interested in determining the effect of lung injury initiated by superoxide anions and hydroxyl radicals on removal of 5-hydroxytryptamine (5-HT) and phenylethylamine by the isolated perfused lung. The rate of removal and percentage of removal of these bioamines was determined before and after lung injury initiated by perfusion of the lung with hypoxanthine (HX) and xanthine oxidase (XO) or xanthine oxidase alone for 10 or 30 minutes; free radicals are generated by such treatment. Because of variation in removal of bioamines among lungs of different animals, the effects of lung injury on bioamine removal were determined by calculating the percentage of inhibition of removal using data from the control and test period for each lung. Perfusion of the lung with HX/XO or XO for 10 or 30 minutes significantly inhibited 5-HT removal by 39.5% and 63.3%, respectively. In contrast, only perfusion of the lung for 30 minutes with HX/XO produced inhibition of phenylethylamine uptake (by 54.8%). As uptake of 5-HT is the rate-limiting step in 5-HT removal, these data demonstrate dose (time)-related depression of active 5-HT uptake by free radicals generated in vitro. The rate-limiting step of phenylethylamine uptake, metabolism by monoamine oxidase, is inhibited only by severe lung injury.