Document Detail

Endothelial ET(B) limits vascular remodelling and development of pulmonary hypertension during hypoxia.
MedLine Citation:
PMID:  19672104     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-06
Journal Detail:
Title:  Journal of vascular research     Volume:  47     ISSN:  1423-0135     ISO Abbreviation:  J. Vasc. Res.     Publication Date:  2010  
Date Detail:
Created Date:  2009-12-09     Completed Date:  2009-12-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  16-22     Citation Subset:  IM    
Copyright Information:
Copyright 2009 S. Karger AG, Basel.
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
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MeSH Terms
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
Mice, Inbred C57BL
Mice, Knockout
Muscle, Smooth, Vascular / metabolism*,  physiopathology
Pulmonary Artery / metabolism*,  physiopathology
Receptor, Endothelin B / deficiency,  genetics,  metabolism*
Ventricular Pressure
Grant Support
//Biotechnology and Biological Sciences Research Council; //Wellcome Trust
Reg. No./Substance:
0/Endothelin-1; 0/Receptor, Endothelin B

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