Depression of serotonin clearance by rat lungs during oxygen exposure

Abstract

The effect of oxygen (O2) exposure on the ability of the isolated, perfused rat lung to clear serotonin (5-hydroxytryptamine, 5-HT) from the perfusate was evaluated in normal or vitamin E-deficient Sprague-Dawley rats. Rats were exposed to 100% O2 at 1 ATA for 4–48 h. Lungs were subsequently isolated, artificially ventilated, and perfused in a recirculating system with Krebs-Ringer bicarbonate solution, pH 7.4 containing 3% bovine serum albumin and 0.25 muM [14C] 5-HT. 5HT clearance was calculated from the disappearance rate of [ 14C] 5-HT from the perfusate. In normal rats exposed to 100% O2, there was a progressive reduction in the clearance of 5-HT with increasing duration of O2 exposure. Compared to lungs from air-exposed controls, clearance was depressed 20% (P less than 0.01) after 18 h, 22% (P less than 0.01) after 24 h, and 35% (P less than 0.001) after 48 h. With vitamin E-deficient rats, the reduction in 5-HT clearance occurred after a shorter exposure time and was of greater magnitude than in rats on a normal diet. Depression of 5HT clearance by the lungs is an early alteration of lung function fue to hyperoxia and is potentiated by vitamin E deficiency. The most likely mechanism for the depression of 5-HT clearance is interference with the transport properties of lung endothelium.