Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension

• Published in: Physiological reviews 2000-10, Vol.80 (4), p.1337-1372
• Main Authors: Hampl, Vaclav, Herget, Jan
• Format: Article
• Language: English
• Subjects: Adult; Anatomy & physiology; Animals; Blood-vessels; Chronic Disease; Chronic illnesses; Disease; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Free Radicals - metabolism; Free Radicals - pharmacology; Gases; Genetic aspects; Health aspects; Humans; Hypertension; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - metabolism; Infant, Newborn; Injuries; Lung - blood supply; Lung - drug effects; Lung - embryology; Lungs; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pulmonary circulation; Pulmonary Circulation - drug effects; Pulmonary Circulation - physiology; Pulmonary hypertension; Vascular Resistance - drug effects; Vascular Resistance - physiology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0031-9333; 1522-1210
• DOI: 10.1152/physrev.2000.80.4.1337

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.