title: Biochemical evidence for pulmonary endothelial cell injury after carbon tetrachloride administration in mice.
abstract: Angiotensin converting enzyme (ACE) is concentrated in pulmonary endothelial cells. Its release into the general circulation after lung damage may provide an index of pulmonary microvascular injury. In the present study, we have examined the effect of the volatile solvent carbon tetrachloride on serum levels of ACE. In mice, a dose-response relationship was obtained in serum ACE 24 hr after acute oral doses of carbon tetrachloride ranging from 0.1 to 2.8 ml/kg. Serum levels of ACE returned to normal by 48 hr after treatment. The increase in serum ACE after carbon tetrachloride treatment correlates with a significant reduction in lung ACE, whereas liver and kidney levels are unaffected. The elevation in serum ACE which occurs after carbon tetrachloride would appear to be, therefore, the result of release from the lungs. Because tissue injury is associated with inflammation, we investigated what effect an anti-inflammatory drug has on the elevation of serum ACE by carbon tetrachloride. Pretreatment of mice with 100 mg/kg of aspirin, orally, produced a 53% reduction in the elevation of serum ACE produced by carbon tetrachloride. These studies strongly suggest that carbon tetrachloride can produce damage to pulmonary endothelial cells. A model to explain the transient nature of elevated serum ACE based on current knowledge of glycoprotein structure and metabolism is proposed.
mesh_terms: D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011292:Premedication
chemical_list: D002251:Carbon Tetrachloride; D007703:Peptidyl-Dipeptidase A; D001241:Aspirin