Effect of glucocorticoids on collagen accumulation in pulmonary vascular remodeling in the rat.
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.
Poiani
G J
GJ
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway.
Tozzi
C A
CA
Thakker-Varia
S
S
Choe
J K
JK
Riley
D J
DJ
D000704:Analysis of Variance; D000818:Animals; D003094:Collagen / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006909:Hydroxyproline / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D008297:Male; D011347:Procollagen / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014221:Triamcinolone / Q000031:analogs & derivatives* / Q000494:pharmacology
D011347:Procollagen; D012333:RNA, Messenger; D014221:Triamcinolone; D003094:Collagen; C030262:triamcinolone diacetate; D006909:Hydroxyproline