Am. J. Respir. Crit. Care Med., Vol 149, No. 4, 04 1994, 994-999.
Effect of glucocorticoids on collagen accumulation in pulmonary vascular remodeling in the rat
GJ Poiani, CA Tozzi, S Thakker-Varia, JK Choe and DJ Riley
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway.
Administration of corticosteroids may attenuate the development of
pulmonary hypertension by inhibiting the cell proliferation and protein
synthesis that occur in early pulmonary vascular remodeling. However, in
vitro studies show that corticosteroids stimulate collagen synthesis in
vascular smooth muscle cells, and corticosteroid administration may be
deleterious in stimulating collagen deposition. To test whether
corticosteroid treatment promotes vascular collagen production in vivo, we
administered triamcinolone diacetate to rats exposed to 10% O2 for 3 days
and measured pro alpha 1(I) collagen mRNA and the hydroxyproline/protein
ratio in the main pulmonary artery. Triamcinolone treatment (12 mg/kg
intraperitoneally, once daily for 3 days) reduced mean right ventricular
pressure (11 +/- 1 versus 14 +/- 1 mm Hg) and protein content of pulmonary
arteries (1.8 +/- 0.1 versus 2.7 +/- 0.1 mg/vessel) (both p < 0.05).
However, corticosteroid treatment produced a dose-related increase in pro
alpha 1(I) mRNA levels and increased the ratio of hydroxyproline/protein
(47 +/- 2 versus 38 +/- 3 micrograms/mg; p < 0.05). Thus, corticosteroid
administration ameliorated the increase in pulmonary hypertension in early
hypoxia, but increased the proportion of collagen in the vessel wall.
Corticosteroid treatment in pulmonary vascular remodeling may be
deleterious in increasing the concentration of collagen in the vessel wall.
