Document Detail

An angiotensin II- and NF-kappaB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension.
MedLine Citation:
PMID:  20110337     Owner:  NLM     Status:  MEDLINE    
AIMS: Connexins (Cxs) play a role in the contractility of the aorta wall. We investigated how connexins of the endothelial cells (ECs; Cx37, Cx40) and smooth muscle cells (SMCs; Cx43, Cx45) of the aorta change during renin-dependent and -independent hypertension.
METHODS AND RESULTS: We subjected both wild-type (WT) mice and mice lacking Cx40 (Cx40(-/-)), to either a two-kidney, one-clip procedure or to N-nitro-l-arginine-methyl-ester treatment, which induce renin-dependent and -independent hypertension, respectively. All hypertensive mice featured a thickened aortic wall, increased levels of Cx37 and Cx45 in SMC, and of Cx40 in EC (except in Cx40(-/-) mice). Cx43 was up-regulated, with no effect on its S368 phosphorylation, only in the SMCs of renin-dependent models of hypertension. Blockade of the renin-angiotensin system of Cx40(-/-) mice normalized blood pressure and prevented both aortic thickening and Cx alterations. Ex vivo exposure of WT aortas, carotids, and mesenteric arteries to physiologically relevant levels of angiotensin II (AngII) increased the levels of Cx43, but not of other Cx. In the aortic SMC line of A7r5 cells, AngII activated kinase-dependent pathways and induced binding of the nuclear factor-kappa B (NF-kappaB) to the Cx43 gene promoter, increasing Cx43 expression.
CONCLUSION: In both large and small arteries, hypertension differently regulates Cx expression in SMC and EC layers. Cx43 is selectively increased in renin-dependent hypertension via an AngII activation of the extracellular signal-regulated kinase and NF-kappaB pathways.
Florian Alonso; Nathalie Krattinger; Lucia Mazzolai; Alexander Simon; Gérard Waeber; Paolo Meda; Jacques-Antoine Haefliger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-28
Journal Detail:
Title:  Cardiovascular research     Volume:  87     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-09-20     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  166-76     Citation Subset:  IM    
Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, University Hospital, CHUV-1011 Lausanne, Switzerland.
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MeSH Terms
Angiotensin II / metabolism*
Angiotensin II Type 1 Receptor Blockers / pharmacology
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Antihypertensive Agents / pharmacology
Aorta / drug effects,  metabolism*,  physiopathology
Binding Sites
Blood Pressure
Carotid Arteries / metabolism,  physiopathology
Cell Line
Connexin 43 / genetics,  metabolism*
Connexins / deficiency,  genetics
Disease Models, Animal
Endothelial Cells / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism
Genes, Reporter
Hypertension, Renovascular / drug therapy,  etiology,  metabolism*,  physiopathology
Mesenteric Arteries / metabolism,  physiopathology
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Smooth Muscle / metabolism
NF-kappa B / metabolism*
NG-Nitroarginine Methyl Ester
Promoter Regions, Genetic
Renin / blood*
Time Factors
Grant Support
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Connexin 43; 0/Connexins; 0/GJA1 protein, mouse; 0/NF-kappa B; 0/connexin 40; 11128-99-7/Angiotensin II; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Signal-Regulated MAP Kinases; EC

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