EFFECT OF GLUCOCORTICOIDS ON COLLAGEN ACCUMULATION IN PULMONARY VASCULAR REMODELING IN THE RAT

Administration of corticosteroids may attenuate the development of pul monary hypertension by inhibiting the cell proliferation and protein s ynthesis that occur in early pulmonary vascular remodeling. However, i n vitro studies show that corticosteroids stimulate collagen synthesis in vascular smooth muscle cells, and corticosteroid administration ma y be deleterious in stimulating collagen deposition. To test whether c orticosteroid treatment promotes vascular collagen production in vivo, we administered triamcinolone diacetate to rats exposed to 10% O-2 fo r 3 days and measured pro alpha 1(l) collagen mRNA and the hydroxyprol ine/protein ratio in the main pulmonary artery. Triamcinolone treatmen t (12 mg/kg intraperitoneally, once daily for 3 days) reduced mean rig ht ventricular pressure (11 +/- 1 versus 14 +/- 1 mm Hg) and protein c ontent of pulmonary arteries (1.8 +/- 0.1 versus 2.7 +/- 0.1 mg/vessel ) (both p < 0.05). However, corticosteroid treatment produced a dose-r elated increase in pro alpha 1(l) mRNA levels and increased the ratio of hydroxyproline/protein (47 +/- 2 versus 38 +/- 3 mu g/mg; p < 0.05) . Thus, corticosteroid administration ameliorated the increase in pulm onary hypertension in early hypoxia, but increased the proportion of c ollagen in the vessel wall. Corticosteroid treatment in pulmonary vasc ular remodeling may be deleterious in increasing the concentration of collagen in the vessel wall.