Effect of asbestos on the metabolism of vasoactive substances in isolated perfused guinea pig lungs.

The measurement of pulmonary metabolism of three vasoactive substances and quantitative assessment of changes in lung morphology were performed in a long-term study of asbestos-exposed guinea pigs. Animals received intratracheal injections of a single dose of a sterile suspension of Canadian chrysotile B (5 mg), while control animals received only saline. Six months after the treatment, the guinea pigs were sacrificed, the lungs removed, perfused via the pulmonary artery and the metabolism of vasoactive substances was assessed (in vitro) in a cascade superfusion system. At the end of the experiments, the lungs were fixed in a glutaraldehyde solution for microscopic examination. The tissue response consisted of both inflammatory reaction of terminal and respiratory bronchioles and diffuse alveolar septal infiltration with interstitial fibrosis. The reaction was characterized at six months by a progressive bronchiolitis obliterans with fibroblastic proliferation and collagen formation. The development of the disease did not cause significant changes in the metabolism of acetylcholine and bradykinin. However, the metabolism of prostaglandin E2 decreased with the appearance of the bronchiolitis obliterans. Our results showed that asbestos exposure may produce early biochemical changes resulting in altered lung metabolism of vasoactive substances; these modifications could contribute to the pathogenesis of asbestosis.