Physiol. Res. 49: 493-501, 2000

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


© 2000 by the Institute of Physiology, Czech Academy of Sciences