Pulmonary interstitial pressure and tissue matrix structure in acute hypoxia. Am J Physiol Lung Cell Mol Physiol 280: L881-L887, 2001.-Pulmonary interstitial pressure was measured via micropuncture in anesthetized rabbits in normoxia and after breathing 12% O 2. In normoxia [arterial PO 2 ϭ 88 Ϯ 2 (SD) mmHg], pulmonary arterial pressure and pulmonary interstitial pressure were 16 Ϯ 8 and Ϫ9.6 Ϯ 2 cmH 2O, respectively. After 6 h of hypoxia (arterial PO2 ϭ 39 Ϯ 16 mmHg), the corresponding values

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... ere 30 Ϯ 8 and 3.5 Ϯ 2.5 cmH 2O (P Ͻ 0.05). Pulmonary interstitial proteoglycan extractability, evaluated by hexuronate assay after 0.4 M guanidinium hydrochloride extraction, was 12.3, 32.4, and 60.6 g/g wet tissue in normoxia and after 3 and 6 h of hypoxia, respectively, indicating a weakening of the noncovalent bonds linking proteoglycans to other extracellular matrix components. Gel filtration chromatography showed an increased fragmentation of chondroitin sulfate-and heparan sulfate-proteoglycans during hypoxic exposure, accounting for a loss of extracellular matrix native architecture and basement membrane structure. Gelatin zymography demonstrated increased amounts of the proteolytically activated form of gelatinase B (matrix metalloproteinase-9) after hypoxic exposure, providing evidence that the activation of proteinases may play a role in hypoxia-induced lung injury. high-altitude pulmonary edema; micropuncture; microvascular permeability; proteoglycans; metalloproteinases