Increase in Anclotensln-Converting Enzyme in Rat Lungs Following Inhalation of Phosgene

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase that catalyzes the conversion of angiotensin I to angiotensin II (a potent vasopressor) and plays an important role in homeostasis of blood pressure as part of the renin-angiotensin-aldosterone system. ACE has been shown to be associated primarily with the luminal surfaces of lung vascular endothelial cells, making it a possible target for the pulmonary toxicant phosgene. Sixty-day-old male Sprague-Dawley rats were exposed to 0.5 ppm phosgene or air for 4 h. Rats were sacrificed immediately and 24 h postexposure. ACE activity was measured in lung, lavage fluid, lavage cell pellets, and serum. Phosgene-exposed rats showed no changes in ACE activity in either lavage fluid or serum compared to air controls, Whole-lung ACE activity was significantly higher immediately and 24 h postexposure to phosgene, with increases of 55% and 44% respectively Phosgene-exposed rats also showed a significant increase in ACE activity in the lavage cell pellets. These increases were 50% and 54% above controls at 0 and 24 h postexposure, respectively. The cell type most likely affected was the alveolar macro-phage. These data suggest that acute exposure to phosgene activates lung ACE, thereby mediating the conversion of angiotensin I to angiotensin II.