Physiological Reviews, Vol. 80, No. 4, October 2000, pp. 1337-1372
Copyright ©2000 by the American Physiological Society
Role of Nitric Oxide in the Pathogenesis of Chronic
Pulmonary Hypertension
Václav
Hampl and
Jan
Herget
Department of Physiology, Charles University Second Medical School,
Prague, Czech Republic
Hampl, Václav and
Jan Herget.
Role of Nitric Oxide in the Pathogenesis of Chronic
Pulmonary Hypertension. Physiol. Rev. 80: 1337-1372, 2000.
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.
