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      Nitric oxide deficiency in pulmonary hypertension: Pathobiology and implications for therapy

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          Abstract

          Nitric oxide (NO) is a diffusible gas with diverse roles in human physiology and disease. Significant progress in the understanding of its biological effects has taken place in recent years. This has led to a better understanding of the pathobiology of pulmonary hypertension (PH) and the development of new therapies. This article provides an overview of the NO physiology and its role in the pathobiology of lung diseases, particularly PH. We also discuss current and emerging specific treatments that target NO signaling pathways in PH.

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          Most cited references 159

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          Nitric oxide as a secretory product of mammalian cells.

          Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.
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            Nitric oxide synthases: roles, tolls, and controls.

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              Primary pulmonary hypertension. A national prospective study.

              A national registry was begun in 1981 to collect data from 32 centers on patients diagnosed by uniform criteria as having primary pulmonary hypertension. Entered into the registry were 187 patients with a mean age (+/- SD) of 36 +/- 15 years (range, 1 to 81), and a female-to-male ratio of 1.7:1 overall. The mean interval from onset of symptoms to diagnosis was 2 years. The most frequent presenting symptoms included dyspnea (60%), fatigue (19%), and syncope (or near syncope) (13%). Raynaud phenomenon was present in 10% (95% of whom were female) and a positive antinuclear antibody test, in 29% (69% female). Pulmonary function studies showed mild restriction (forced vital capacity [FVC], 82% of predicted) with a reduced diffusing capacity for carbon monoxide (DLCO), and hypoxemia with hypocapnia. The mean (+/- SD) right atrial pressure was 9.7 +/- 6 mm Hg; mean pulmonary artery pressure, 60 +/- 18 mm Hg; cardiac index, 2.3 +/- 0.9 L/min X m2; and pulmonary vascular resistance index, 26 +/- 14 mm Hg/L/min X m2 for the group. Although no deaths or sustained morbid events occurred during the diagnostic evaluation of the patients, the typically long interval from initial symptoms to diagnosis emphasizes the need to develop strategies to make the diagnosis earlier.
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                Author and article information

                Journal
                Pulm Circ
                Pulm Circ
                PC
                Pulmonary Circulation
                Medknow Publications & Media Pvt Ltd (India )
                2045-8932
                2045-8940
                Jan-Mar 2013
                : 3
                : 1
                : 20-30
                Affiliations
                [1 ]Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland, Ohio, USA
                [2 ]Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
                [3 ]Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Turkey,
                Author notes
                Address correspondence to: Dr. Raed A. Dweik, Cleveland Clinic, 9500 Euclid Ave. A-90, Cleveland, OH 44195, USA dweikr@ 123456ccf.org
                Article
                PC-3-20
                10.4103/2045-8932.109911
                3641730
                23662172
                Copyright: © Pulmonary Circulation

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Review Article

                Respiratory medicine

                physiopathology and therapeutics, nitric oxide, pulmonary hypertension

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