Pulmonary interstitial pressure and tissue matrix structure in acute hypoxia.
Pulmonary interstitial pressure was measured via micropuncture in anesthetized rabbits in normoxia and after breathing 12% O(2). In normoxia [arterial PO(2) = 88 +/- 2 (SD) mmHg], pulmonary arterial pressure and pulmonary interstitial pressure were 16 +/- 8 and -9.6 +/- 2 cmH(2)O, respectively. After 6 h of hypoxia (arterial PO(2) = 39 +/- 16 mm Hg), the corresponding values were 30+/-8 and 3.5+/-2.5 cm H(2)O (P<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 microg/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.
Miserocchi
G
G
Department of Experimental and Environmental Medicine and Biotechnology, University of Milano-Bicocca, 20052 Monza, Italy. giuseppe.miserocchi@unimib.it
Passi
A
A
Negrini
D
D
Del Fabbro
M
M
De Luca
G
G
D000818:Animals; D001794:Blood Pressure; D002809:Chondroitin Sulfates / Q000378:metabolism; D002850:Chromatography, Gel; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006603:Hexuronic Acids / Q000032:analysis; D006874:Hydrostatic Pressure; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007366:Intercostal Muscles / Q000503:physiopathology; D008168:Lung / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008970:Molecular Weight; D009929:Organ Size; D011651:Pulmonary Artery / Q000503:physiopathology; D011817:Rabbits
D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D006603:Hexuronic Acids; D020780:Matrix Metalloproteinase 9