Document Detail


Activation of resistance arteries with endothelin-1: from vasoconstriction to functional adaptation and remodeling.
MedLine Citation:
PMID:  15017111     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Remodeling of resistance arteries is a key feature in hypertension. We studied the transition of vasoconstriction to remodeling in isolated rat skeletal muscle arterioles. Arterioles activated with 10 nM endothelin-1 showed functional adaptation when kept at low distension in a wire myograph setup, where contractile properties shifted towards a smaller lumen diameter after 1 day. Pressurized arteries kept in organoid culture showed physical inward remodeling after 3-day activation with 10 nM endothelin-1, characterized by a reduction in relaxed diameter without a change in the wall cross-sectional area (eutrophic remodeling). The relaxed lumen diameter (at 60 mm Hg) decreased from 169 +/- 5 (day 0) to 155 +/- 4 microm (day 3). An antibody directed to the beta(3)-integrin subunit (but not one directed to the beta(1)-integrin subunit) enhanced remodeling, from a reduction in relaxed diameter at 60 mm Hg of 15 +/- 2.4 to 22 +/- 1.8 microm (both on day 3). Collagen gel contraction experiments showed that the antibody directed to the beta(3)-integrin subunit enhanced the compaction of collagen by smooth muscle cells, from 83 +/- 1.5 to 68 +/- 1.5% of the initial gel diameter. In conclusion, these data show that inward eutrophic remodeling is a response to sustained contraction, which may involve collagen reorganization through beta(3)-integrins.
Authors:
Erik N T P Bakker; Carsten L Buus; Ed VanBavel; Michael J Mulvany
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-03-12
Journal Detail:
Title:  Journal of vascular research     Volume:  41     ISSN:  1018-1172     ISO Abbreviation:  J. Vasc. Res.     Publication Date:    2004 Mar-Apr
Date Detail:
Created Date:  2004-04-15     Completed Date:  2004-05-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  174-82     Citation Subset:  IM    
Copyright Information:
Copyright 2004 S. Karger AG, Basel
Affiliation:
Department of Pharmacology, University of Aarhus, Aarhus, Denmark. n.t.bakker@amc.uva.nl
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / drug effects,  physiology*
Animals
Antibodies, Monoclonal / pharmacology
Antigens, CD29 / immunology,  metabolism
Aorta / cytology,  metabolism*
Endothelin-1 / pharmacology*
Extracellular Matrix / metabolism
Integrin beta3 / immunology,  metabolism
MAP Kinase Signaling System / drug effects,  physiology
Male
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Muscle, Smooth, Vascular / cytology,  enzymology*
Organ Culture Techniques
Rats
Rats, Wistar
Vascular Resistance / drug effects,  physiology*
Vasoconstriction / drug effects,  physiology*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD29; 0/Endothelin-1; 0/Integrin beta3; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases

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