Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma

The walls of pulmonary capillaries are extremely thin, and wall stress incr eases greatly when capillary pressure rises. Alveolar hypoxia causes pulmon ary vasoconstriction and hypertension, and if this is uneven, some capillar ies may be exposed to high transmural pressure and develop stress failure. There is evidence that increased wall stress causes capillary remodeling. I n this study we exposed Madison strain Sprague-Dawley rats to normobaric hy poxia (10% oxygen) for 6 h or 3 d (short-term group), and for 3 d or 10 d ( long-term group). Peripheral lung tissue was then collected and messenger R NA (mRNA) levels were determined for extracellular matrix (ECM) proteins an d growth factors. Collagen content (hydroxyproline) was also measured. Leve ls of mRNA for alpha 2(IV) procollagen increased sixfold after 6 h of hypox ia and sevenfold after 3 d of hypoxia, and then decreased after 10 d exposu re. Levels of mRNA for platelet-derived growth factor-B (PDGF-B) doubled af ter 6 h of hypoxia but returned to control values after 3 d. mRNA levels fo r alpha 1(I) and alpha 1(III) procollagens and fibronectin were increased a fter 3 d of hypoxia (by seven- to 12-fold, 1.6- to eightfold, and 12-fold, respectively), then decreased toward control values after 10 d. In contrast , neither levels of mRNA for vascular endothelial growth factor (VEGF) nor collagen content changed. These results suggest that alveolar hypoxia cause s vascular remodeling in lung parenchyma, and are consistent with capillary wall remodeling in response to increased wall stress.