Effect of continuous beta-blockade on collagen synthesis in interstitial fibroblasts isolated from adult rat lung. An in vitro model of progressive pulmonary fibrogenesis.
Continuous administration of propranolol to adult rats resulted in pulmonary changes indicative of fibrogenesis in the absence of an extensive inflammatory infiltrate. Interstitial fibroblasts, isolated from the lungs of rats continuously exposed to 0.5 mg propranolol-HCl/hr via subcutaneous osmotic pumps for 1 or 3 wk synthesized more acid-insoluble collagenase-sensitive protein than matched controls. This effect could be decreased, but not prevented, by administering zinc salts to the animals in drinking-water during drug treatment. A larger percentage of the overall protein synthesis of the propranolol-treated cells was devoted to collagenous proteins as well. Isolated fibroblasts placed in tissue culture and treated with propranolol secreted more total lactate dehydrogenase than controls; this change was due to increased secretion of lactate dehydrogenase isoenzyme 5. Three weeks of propranolol treatment caused a 31% decrease in the number of beta-adrenergic lung receptors, with no change in their affinity. These results suggest that this in vitro model may be useful in elucidating mechanisms of progressive lung disease following long-term exposure to injurious agents.
Smith
S K
SK
Division of Science, College of Basic Studies, Boston University, 871 Commonwealth Avenue, Boston, MA 02215 USA.
Smith
D M
DM