Qualitative changes of vascular wall matrix collagens in chronic hypoxic pulmonary hypertension were studied by gel electrophoresis. Male adult rats (n = 12) were exposed to hypoxia (FiO2 = 0.1, 3 wks). Control rats (n = 13) were kept in air. Samples of peripheral pulmonary arteries (PPA, diam. 100-400 microm), main branches of pulmonary artery, and aorta were dissected. Arterial samples were treated with 4M guanidine-HCl to remove noncollagenous moieties and the collagenous stroma was dissolved by limited pepsin digestion at low pH. Low molecular mass peptides (M. W. approx. 76 and 66 kD) were detected in the gel electrophoretic profile of collagen peptides of PPA of the chronically hypoxic animals and in aorta of both hypoxic and normoxic groups. These peptides were absent in the PPA of normoxic rats. Since the 76 kD peptide bound anticollagen type I antibodies, it appears to be of collagenous nature and it may be the result of collagenolytic activity in PPA isolated from hypoxic lungs. This was confirmed by zymography. We conclude that exposure of rats to chronic hypoxia results in the presence of low molecular mass peptides in the wall matrix of PPA which resemble those found in aorta of normoxic animals. Collagenolytic activity in the walls of peripheral pulmonary arteries may participate in the mechanism of lung vascular remodelling in chronic hypoxia.

Department of Medical Chemistry and Biochemistry 2nd Medical School Charles University Prague Czech Republic

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Mechanisms Controlling the Behavior of Vascular Smooth Muscle Cells in Hypoxic Pulmonary Hypertension

Decreased collagen VI in the tunica media of pulmonary vessels during exposure to hypoxia: a novel step in pulmonary arterial remodeling