| Endothelial ET(B) limits vascular remodelling and development of pulmonary hypertension during hypoxia. | |
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MedLine Citation:
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PMID: 19672104 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: We hypothesised that the potential protective effects of endothelial ET(B) are important in limiting pulmonary vascular muscularisation, vasoconstriction and the development of pulmonary arterial hypertension in response to hypoxia. METHODS: EC-specific ET(B) knockout mice (EC ET(B)(-/-)) and control mice (ET(B)(f/f)) were subjected to hypobaric hypoxic (10% FiO2) or normoxic conditions for 14 days before assessment of right ventricular pressure and pulmonary vascular morphology and function. RESULTS: During normoxia, no difference in right ventricular pressure was detected between EC ET(B)(-/-) (23.7 +/- 1.7 mm Hg) and ET(B)(f/f) mice (20.2 +/- 1.5 mm Hg). Hypoxia induced an exaggerated increase in right ventricular pressure in EC ET(B)(-/-) mice (34.4 +/- 1.2 mm Hg vs. 24.6 +/- 1.4 mm Hg), accompanied by an increase in right ventricular mass. No effect was observed in ET(B)(f/f) mice. Endothelin-1 constricted pulmonary arteries from both groups, although maximum response was similar irrespective of inspired oxygen or genotype. Hypoxia increased the percentage of muscularised vessels in both groups of mice, but the percentage increase was significantly greater in EC ET(B)(-/-) mice. CONCLUSIONS: The potential protective effects of endothelial ET(B) are important in limiting pulmonary vascular muscularisation and the development of pulmonary arterial hypertension in response to hypoxia. |
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Authors:
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N F Kelland; A J Bagnall; I Morecroft; F H Gulliver-Sloan; Y Dempsie; M Nilsen; M Yanagisawa; M R Maclean; Y V Kotelevtsev; D J Webb |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-06 |
Journal Detail:
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Title: Journal of vascular research Volume: 47 ISSN: 1423-0135 ISO Abbreviation: J. Vasc. Res. Publication Date: 2010 |
Date Detail:
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Created Date: 2009-12-09 Completed Date: 2009-12-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9206092 Medline TA: J Vasc Res Country: Switzerland |
Other Details:
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Languages: eng Pagination: 16-22 Citation Subset: IM |
Copyright Information:
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Copyright 2009 S. Karger AG, Basel. |
Affiliation:
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Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / complications, metabolism*, physiopathology Blood Pressure Disease Models, Animal Endothelin-1 / metabolism* Endothelium, Vascular / metabolism*, physiopathology Hypertension, Pulmonary / etiology, metabolism, physiopathology, prevention & control* Hypertrophy, Right Ventricular / etiology, metabolism, prevention & control Male Mice Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular / metabolism*, physiopathology Pulmonary Artery / metabolism*, physiopathology Receptor, Endothelin B / deficiency, genetics, metabolism* Vasoconstriction Ventricular Pressure |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council; //Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Endothelin-1; 0/Receptor, Endothelin B |
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