Role of reactive oxygen species and nitric oxide in development of the hypoxic pulmonary hypertension
Abstract
Pulmonary circulation is completely different compared to systemic circulation. Chronic hypoxia damages peripheral pulmonary arterioles and causes hypoxic pulmonary hypertension (HPH) which consists of vasoconstriction and remodelling of the arterioles.
The release of reactive oxygen species (ROS) - mainly superoxide and nitric oxide (NO) contribute to the pathogenesis of HPH. During exposition to chronic hypoxia, the NO production is markedly elevated and it has two effects: the first, direct vasodilatory effect caused by NO, the second, contribution to remodelling of the peripheral pulmonary vessels by interaction with ROS.
The interaction of superoxid and NO releases peroxynitrite which plays a role in the onset of collagen cleavage. A typical low molecular weight of collagen fragments induces remodelling of the peripheral pulmonary arterioles.
These changes are typical for the first week of exposure to the chronic hypoxia which also correlates with sudden elevation of the mean pulmonary artery pressure. Continual exposition to the chronic hypoxia after first week does not cause progressive worsening of HPH.