Assessment of bleomycin lung toxicity using angiotensin-converting enzyme in pulmonary lavage.

Abstract

Activity of the dipeptidyl hydrolase angiotensin-converting enzyme has been observed to be altered by treatment with bleomycin. We used an animal model of bleomycin lung toxicity to study the effects on angiotensin-converting enzyme activity in various lung fractions. Serum activity of angiotensin-converting enzyme increased only 23% after a single intratracheal instillation of bleomycin. Lung tissue angiotensin-converting enzyme activity fell to 40% of control level (p < 0.05) and returned toward and eventually exceeded control values during the ensuing 6 weeks. However, angiotensin-converting enzyme activity in alveolar lavage fluid from bleomycin-treated rats was elevated 30-fold above the barely detectable levels found in control animals. Angiotensin-converting enzyme activity in lavage fluid was soluble and was not associated with the alveolar cell pellet. Maximum elevation of lavage angiotensin-converting enzyme activity occurred 3 days following bleomycin instillation. Significant transudation of serum into alveolar lavage fluid occurred in bleomycin-treated rats. Nevertheless, this phenomenon would not explain the high levels of angiotensin-converting enzyme activity found in lavage fluid. Elevated lavage angiotensin-converting enzyme levels were detected after doses of bleomycin too low to cause significant sequelae of pulmonary fibrosis. Lavage angiotensin-converting enzyme is a sensitive monitor of tissue response to bleomycin.