Time course of hypoxia-induced lung injury in rats.
We investigated the effects of normobaric hypoxia on rat lungs and hypothesized that the hypoxic exposure would induce lung injury with pulmonary edema and inflammation ensued by development of fibrosis. Rats were exposed to 10% O(2) in nitrogen over 6-168h. We analyzed cardiovascular function and pulmonary changes, lung histology and mRNA expression of extracellular matrix (ECM) molecules in the lung. Significant hemodynamic changes occurred after 168h of hypoxic exposure. Moderate pulmonary edema appeared after 8h and peaked after 16h of hypoxia. It was accompanied by inflammation, fibrosis and vascular hypertrophy. mRNA expression of transforming growth factor-beta2 and -beta3 was up-regulated in lung tissue after 8h of hypoxia. After 8-16h, mRNA expression of collagen types I and III and of other ECM molecules was significantly elevated and increased further with longer exposure to hypoxia. The time course of hypoxia-induced pulmonary injury resembled that previously observed after continuous norepinephrine infusion in rats.
Rassler
Beate
B
Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstr. 27, D-04103 Leipzig, Germany. rasb@medizin.uni-leipzig.de
Marx
Grit
G
Reissig
Christian
C
Rohling
Marc A
MA
Tannapfel
Andrea
A
Wenger
Roland H
RH
Zimmer
Heinz-Gerd
HG
D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D015870:Gene Expression; D006352:Heart Ventricles / Q000473:pathology; D000860:Hypoxia / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008168:Lung / Q000473:pathology*; D055370:Lung Injury; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3