HYPEROXIA INHIBITS PROLIFERATION OF CULTURED RAT TRACHEAL SMOOTH-MUSCLE CELLS

Exposure of the lung to elevated oxygen leads to structural and cellul ar injury followed by extensive tissue remodeling. In vitro models uti lizing isolated cells exposed to hyperoxic conditions or exogenously a dded oxidants may be injurious or stimulatory depending on the specifi c cell type and level and duration of exposure. In the present study, proliferation of cultured rat tracheal smooth muscle cells was inhibit ed by oxygen concentrations of 40 and 70% compared with a ''normoxic'' concentration of 21%. Exposure to 70% oxygen had a hypertrophic effec t on the cells, as indicated by increased cellular protein content, wh ereas cells exposed to 21% oxygen did not show increased protein conte nt. Exogenously added oxidant, H2O2, resulted in complete inhibition o f growth of tracheal smooth muscle cells at concentrations > 3 mu M. M uch higher concentrations of H2O2 were required to inhibit proliferati on of vascular smooth muscle cells and rat lung fibroblasts. The heigh tened sensitivity of airway smooth muscle cells to oxygen and oxidants may be an important factor in the early events following hyperoxia-in duced lung injury.