| Transpulmonary Flux of S-Nitrosothiols and Pulmonary Vasodilation During Nitric Oxide Inhalation: Role of Transport. | |
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MedLine Citation:
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PMID: 22323364 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Inhaled NO (iNO) is used to treat pulmonary hypertension and is being investigated for prevention of bronchopulmonary dysplasia in neonates. Extrapulmonary effects of iNO are widely recognized, but the underlying chemistry and pharmacology are poorly understood. Growing evidence suggests that, in addition to diffusion of NO, NO-derived nitrosants can react in the alveolar lining fluid with endogenous L-cysteine (L-Cys), with conversion to the S-nitrosothiol (SNO) SNO-L-cysteine (CSNO). CSNO can then enter cells via the amino acid transporter type L (LAT). To determine the influence of LAT and supplemental L-Cys on the functional activity of iNO and transpulmonary movement of SNOs or other related species, we exposed C57Bl6 mice to nebulized L-Cys or D-Cys and/or LAT competitors. Isolated lungs were then perfused with physiologic buffer while effluent was collected to assay perfusate SNOs. Nebulized L-Cys, but not D-Cys, augmented the iNO-induced increase in circulating SNOs in the effluent without altering iNO-induced pulmonary vasodilation. Addition to the perfusate of either L-leucine (L-Leu) or 2-amino-2-norborane carboxylic acid (BCH), two distinct LAT competitors, inhibited appearance in the perfusate of SNOs in L-Cys-exposed lungs; a higher concentration of L-Leu significantly inhibited the iNO-induced pulmonary vasodilation as well as SNO accumulation. We conclude that iNO-induced pulmonary vasodilation and the transpulmonary movement of iNO-derived SNOs are mediated in part by formation of extracellular CSNO, uptake by alveolar epithelial LAT, and /or export by LAT from the pulmonary endothelium into the circulation. Therapies that exploit and optimize LAT-dependent SNO transport might improve the efficacy of and clinical outcomes with iNO by improving systemic SNO delivery. |
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Authors:
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Jordan A Torok; Mulugu V Brahmajothi; Hongmei Zhu; Brian T Tinch; Richard L Auten; Timothy J McMahon |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-9 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: - ISSN: 1535-4989 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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