EFFECT OF ALPHA-NAPHTHYLTHIOUREA ON UPTAKE OF 5-HYDROXYTRYPTAMINE FROM THE PULMONARY CIRCULATION

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Abstract
Pulmonary injury caused by .alpha.-naphthylthiourea (ANTU) [rodenticide] was characterized by alterations of capillary endothelial barrier followed by lung edema. Because pulmonary uptake of 5-hydroxytryptamine (5-HT) was dependent on active transcellular transport by lung endothelium, it may be an index of early impairment of endothelial function caused by ANTU. Effect of a single i.p. dose of 5 or 10 mg/kg ANTU on pulmonary uptake of 5-HT by isolated rat lungs was studied. After administration of ANTU (4 h), when lung tissue structure and dry-to-wet-weight ratios were comparable to those of controls, 5-HT uptakes were significantly reduced (P < 0.05). After administration of ANTU (24 h), when lung edema was present on histologic examination and by lung weights, 5-HT uptakes were further reduced. They returned to control values 14 days after administration of ANTU. Depression of 5-HT uptake was an early and reversible alteration of lung endothelial cell function caused by ANTU. Uptake of 5-HT may provide a sensitive probe with which to detect and evaluate pulmonary endothelial cell injury caused by toxicants.