| Alterations in lung arginine metabolism in lambs with pulmonary hypertension associated with increased pulmonary blood flow. | |
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MedLine Citation:
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PMID: 19818875 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies demonstrate impaired nitric oxide (NO) signaling in children and animal models with congenital heart defects and increased pulmonary blood flow. However, the molecular mechanisms underlying these alterations remain incompletely understood. The purpose of this study was to determine if early changes in arginine metabolic pathways could play a role in the reduced NO signaling demonstrated in our lamb model of congenital heart disease with increased pulmonary blood flow (Shunt lambs). The activities of the arginine recycling enzymes, argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) were both decreased in lung tissues of Shunt lambs while arginase activity was increased. Associated with these alterations, lung L-arginine levels were decreased. These changes correlated with an increase in NO synthase-derived reactive oxygen species (ROS) generation. This study provides further insights into the molecular mechanisms leading to decreased NO signaling in Shunt lambs and suggests that altered arginine metabolism may play a role in the development of the endothelial dysfunction associated with pulmonary hypertension secondary to increased pulmonary blood flow. |
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Authors:
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Shruti Sharma; Sanjiv Kumar; Neetu Sud; Dean A Wiseman; Jing Tian; Imran Rehmani; Sanjeev Datar; Peter Oishi; Sohrab Fratz; Richard C Venema; Jeffrey R Fineman; Stephen M Black |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-10-08 |
Journal Detail:
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Title: Vascular pharmacology Volume: 51 ISSN: 1879-3649 ISO Abbreviation: Vascul. Pharmacol. Publication Date: 2009 Nov-Dec |
Date Detail:
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Created Date: 2009-11-16 Completed Date: 2010-01-20 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101130615 Medline TA: Vascul Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 359-64 Citation Subset: IM |
Affiliation:
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Vascular Biology Center, 1459 Laney Walker Boulevard, CB3201B, Medical College of Georgia, Augusta, GA 30912, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Amino Acids / blood Animals Arginase / metabolism Arginine / metabolism* Blood Pressure Female Hypertension, Pulmonary / metabolism* Lung / metabolism* Molecular Sequence Data Nitric Oxide / physiology Pregnancy Pulmonary Circulation* Sheep |
| Grant Support | |
ID/Acronym/Agency:
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1K99HL097153/HL/NHLBI NIH HHS; F32 HL090198-01A1/HL/NHLBI NIH HHS; HL084739/HL/NHLBI NIH HHS; HL60190/HL/NHLBI NIH HHS; HL61284/HL/NHLBI NIH HHS; HL67841/HL/NHLBI NIH HHS; HL70061/HL/NHLBI NIH HHS; HL72123/HL/NHLBI NIH HHS; R01 HL060190-11A1/HL/NHLBI NIH HHS; R01 HL060190-12/HL/NHLBI NIH HHS; R01 HL067841-09/HL/NHLBI NIH HHS; R01 HL067841-10/HL/NHLBI NIH HHS; R01 HL070061-05/HL/NHLBI NIH HHS; R01 HL084739-03W1/HL/NHLBI NIH HHS; R01 HL084739-04/HL/NHLBI NIH HHS; R21 HD057406-02/HD/NICHD NIH HHS; R21HD057406/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 10102-43-9/Nitric Oxide; 74-79-3/Arginine; EC 3.5.3.1/Arginase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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