MINIREVIEW
A Possible Role of the Oxidant Tissue Injury in the Development of Hypoxic
Pulmonary Hypertension
J. Herget, J. Wilhelm1, J. Novotná1,
A. Eckhardt, R. Vytášek, L. Mrázková, M. Ošťádal
Department of Physiology and 1Department of Medical Chemistry and
Biochemistry, Second Faculty of Medicine, Charles University, Prague, Czech
Republic
Received February 29, 2000
Accepted April 3, 2000
Summary
Chronic sojourn in hypoxic environment results in the
structural remodeling of peripheral pulmonary arteries and pulmonary
hypertension. We hypothesize that the pathogenesis of changes in pulmonary
vascular structure is related to the increase of radical production induced by
lung tissue hypoxia. Hypoxia primes alveolar macrophages to produce more
hydrogen peroxide. Furthermore, the increased release of oxygen radicals by
other hypoxic lung cells cannot be excluded. Several recent reports demonstrate
the oxidant damage of lungs exposed to chronic hypoxia. The production of nitric
oxide is high in animals with hypoxic pulmonary hypertension and the serum
concentration of nitrotyrosine (radical product of nitric oxide and superoxide
interaction) is also increased in chronically hypoxic rats. Antioxidants were
shown to be effective in the prevention of hypoxia induced pulmonary
hypertension. We suppose that the mechanism by which the radicals stimulate of
the vascular remodeling is due to their effect on the metabolism of vascular
wall matrix proteins. Non-enzymatic protein alterations and/or activation of collagenolytic matrix metalloproteinases may also participate. The presence of
low-molecular weight cleavage products of matrix proteins stimulates the mesenchymal proliferation in the wall of distal pulmonary arteries. Thickened
and less compliant peripheral pulmonary vasculature is then more resistant to
the blood flow and the hypoxic pulmonary hypertension is developed.
Key words
Pulmonary hypertension · Chronic
hypoxia · Pulmonary vasculature ·
Structural remodeling · Oxygen free radicals · Nitrotyrosine
Reprint requests
Dr. Jan Herget, Department of Physiology, Second Faculty of
Medicine, Charles University, Prague, Plzeňská 221, 150 06 Praha 5,
Czech Republic, e-mail: Jan.Herget@lfmotol.cuni.cz
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