Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension

被引:208
作者
Hampl, V [1 ]
Herget, J [1 ]
机构
[1] Charles Univ Prague, Sch Med 2, Dept Physiol, Prague 15000 5, Motol, Czech Republic
关键词
D O I
10.1152/physrev.2000.80.4.1337
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Chronic pulmonary hypertension is a serious complication of a number of chronic lung and heart diseases. In addition to vasoconstriction, its pathogenesis includes injury to the peripheral pulmonary arteries leading to their structural remodeling. Increased pulmonary vascular synthesis of an endogenous vasodilator, nitric oxide (NO), opposes excessive increases of intravascular pressure during acute pulmonary vasoconstriction and chronic pulmonary hypertension, although evidence for reduced NO activity in pulmonary hypertension has also been presented. NO can modulate the degree of vascular injury and subsequent fibroproduction, which both underlie the development of chronic pulmonary hypertension. On one hand, NO can interrupt vascular wall injury by oxygen radicals produced in increased amounts in pulmonary hypertension. NO can also inhibit pulmonary vascular smooth muscle and fibroblast proliferative response to the injury. On the other hand, NO may combine with oxygen radicals to yield peroxynitrite and other related, highly reactive compounds. The oxidants formed in this manner may exert cytotoxic and collagenolytic effects and, therefore, promote the process of reparative vascular remodeling. The balance between the protective and adverse effects of NO is determined by the relative amounts of NO and reactive oxygen species. We speculate that this balance may be shifted toward more severe injury especially during exacerbations of chronic diseases associated with pulmonary hypertension. Targeting these adverse effects of NO-derived radicals on vascular structure represents a potential novel therapeutic approach to pulmonary hypertension in chronic lung diseases.
引用
收藏
页码:1337 / 1372
页数:36
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