Hyperoxia and
Recovery from Hypoxia Alter Collagen in
Peripheral Pulmonary Arteries Similarly
J. NOVOTNÁ1, J. BÍBOVÁ2, V. HAMPL2, Z. DEYL3, J. HERGET2
1Department
of Biochemistry, 2Department
of Physiology, Second Medical School, Charles
University, 3Institute
of Physiology, Czech Academy of Sciences and 1,2Centre for
Experimental Cardiovascular Research, Prague,
Czech Republic
Received
March 20, 2000
Accepted August 4, 2000
Summary
Chronic hypoxia causes pulmonary hypertension,
the mechanism of which includes altered collagen
metabolism in the pulmonary vascular wall. This
chronic hypoxic pulmonary hypertension is
gradually reversible upon reoxygenation. The
return to air after the adjustment to chronic
hypoxia resembles in some aspects a hyperoxic
stimulus and we hypothesize that the changes of
extracellular matrix proteins in peripheral
pulmonary arteries may be similar. Therefore, we
studied the exposure to moderate chronic
hyperoxia (FiO2 = 0.35, 3 weeks) in rats and
compared its effects on the rat pulmonary
vasculature to the effects of recovery (3 weeks)
from chronic hypoxia (FiO2 = 0.1, 3 weeks).
Chronically hypoxic rats had pulmonary
hypertension (Pap = 26±3 mm Hg, controls 16±1
mm Hg) and right ventricular hypertrophy.
Pulmonary arterial blood pressure and right
ventricle weight normalized after 3 weeks of
recovery in air (Pap = 19±1 mm Hg). The rats
exposed to moderate chronic hyperoxia also did
not have pulmonary hypertension
(Pap = 18±1 mm Hg, controls 17±1 mm Hg).
Collagenous proteins isolated from the peripheral
pulmonary arteries (100-300 mm) were studied
using polyacrylamide gel electrophoresis. A
dominant low molecular weight peptide (approx. 76
kD) was found in hypoxic rats. The proportion of
this peptide decreases significantly in the
course of recovery in air. In addition, another
larger peptide doublet was found in rats
recovering from chronic hypoxia. It was localized
in polyacrylamide gels close to the zone of a2
chain of collagen type I. It was bound to
anticollagen type I antibodies. An identically
localized peptide was found in rats exposed to
moderate chronic hyperoxia. The apparent
molecular weight of this collagen fraction
suggests that it is a product of collagen type I
cleavage by a rodent-type interstitial
collagenase (MMP-13). We conclude that chronic
moderate hyperoxia and recovery from chronic
hypoxia have a similar effect on collagenous
proteins of the peripheral pulmonary arterial
wall.
Key
words
Chronic hypoxia ·
Chronic hyperoxia · Collagen ·
Metalloproteinases · Vascular remodeling ·
Pulmonary hypertension · Rat
Reprint requests
Prof. Jan Herget, MD,
Department of Physiology, Second Medical School,
Charles University, Plzeòská 221, 150 00
Prague, Czech Republic. Jan.Herget@lfmotol.cuni.cz
|
