CIGARETTE-SMOKE CAUSES RAPID CELL-PROLIFERATION IN SMALL AIRWAYS AND ASSOCIATED PULMONARY-ARTERIES

To determine whether smoke could directly affect the cells of the smal l airways and the small vessels, we exposed Sprague-Dawley rats to the whole smoke of 7 cigarettes/day for 1, 2, or 7 days. Three hours befo re the rats were killed, 5-bromo-2'-deoxyuridine (BrdU) was administer ed. Labeled nuclei were counted in histological sections stained with antibodies to BrdU. In smokers, pulmonary artery walls at the level of the membranous bronchioles (MB), respiratory bronchioles (RB), and al veolar ducts (AD) showed significant increases in labeled nuclei at al l three times; increases in endothelial labeling were only present in vessels associated with AD. Significantly increased labeling was also seen in the epithelium and walls of MB and RB themselves at all time p eriods. However, there was no correlation between labeling indexes in matched pairs of airways and vessels. Smoke had no effect on the label ing of mesothelial and submesothelial cells. We conclude that cigarett e smoke rapidly causes proliferation of intrinsic cells in the airways and small vessels; this effect may lead eventually to airway wall mus cular hyperplasia and fibrosis (small airways disease) and to vascular changes associated with pulmonary hypertension. However, the lack of correlation between labeling indexes in the vessels and airways sugges ts that different mediators are involved at these two sites. At least over the time course of this experiment, smoke does not cause prolifer ation of mesothelial or submesothelial cells.