Depression of serotonin uptake by rat lungs exposed to paraquat.
Paraquat is a widely used herbicide which causes lung injury in animals and humans. To determine whether pulmonary endothelial cell function is altered during the course of paraquat lung toxicity, we measured uptake of serotonin in isolated perfused lungs from rats injected i.p. with 25 mg/kg of paraquat dichloride. In 38 control lungs, serotonin uptake was 0.71 +/- 0.02 (S.E.) and was not significantly different in rats studied 4 and 18 hr after paraquat administration. In contrast, uptakes were 0.60 +/- 0.04 (P less than .05) 24 hr after injection of paraquat. At that time, lung histology and endothelial ultrastructure were unremarkable and dry-to-wet-weight ratios of lungs were normal. Forty-eight hours after paraquat administration, when light and electron microscope evidence of edema and inflammation were extensive, serotonin uptake was further decreased (P less than .01). Two weeks after injection of paraquat, when fibrosis was present, based on lung histology and hydroxyproline content, serotonin uptakes had returned to control levels. Administration of superoxide dismutase prolonged survival but did not protect against paraquat-induced depression of serotonin uptake. These results indicate that paraquat causes an early and reversible depression of pulmonary endothelial cell uptake of serotonin which antedates morphological alterations in lung and the endothelial cell and which is not prevented by treatment with exogenous superoxide dismutase. Uptake of serotonin may provide a sensitive and specific index of injury to the pulmonary endothelium.
D000818:Animals; D003864:Depression, Chemical; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D012701:Serotonin; D013482:Superoxide Dismutase; D010269:Paraquat; D006909:Hydroxyproline