S-nitrosothiol repletion by an inhaled gas regulates pulmonary function

Citation
Mp. Moya et al., S-nitrosothiol repletion by an inhaled gas regulates pulmonary function, P NAS US, 98(10), 2001, pp. 5792-5797
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
98
Issue
10
Year of publication
2001
Pages
5792 - 5797
Database
ISI
SICI code
0027-8424(20010508)98:10<5792:SRBAIG>2.0.ZU;2-P
Abstract
NO synthases are widely distributed in the lung and are extensively involve d in the central of airway and vascular homeostasis, It is recognized, howe ver, that the O-2-rich environment of the lung may predispose NO toward tox icity. These Janus faces of NO are manifest in recent clinical trials with inhaled NO gas, which has shown therapeutic benefit in some patient populat ions but increased morbidity in others. In the airways and circulation of h umans, most NO bioactivity is packaged in the form of S-nitro-sothiols (SNO s), which are relatively resistant to toxic reactions with O-2/O-2(-). This finding has led to the proposition that channeling of NO into SNOs may pro vide a natural defense against lung toxicity. The means to selectively mani pulate the SNO pool, however, has not been previously possible. Here we rep ort on a gas, O-nitrosoethanol (ENO), which does not react with Oz or relea se NO and which markedly increases the concentration of indigenous species of SNO within airway lining fluid. Inhalation of ENO provided immediate rel ief from hypoxic pulmonary vasoconstriction without affecting systemic hemo dynamics. Further, in a porcine model of lung injury, there was no rebound in cardiopulmonary hemodynamics or fall in oxygenation on stopping the drug (as seen with NO gas), and additionally ENO protected against a decline in cardiac output. Our data suggest that SNOs within the lung serve in matchi ng ventilation to perfusion, and can be manipulated for therapeutic gain. T hus, ENO may be of particular benefit to patients with pulmonary hypertensi on, hypoxemia, and/or right heart failure, and may offer a new therapeutic approach in disorders such as asthma and cystic fibrosis, where the airways may be depleted of SNOs.