A mouse model of targeted deletion of the calcium sensing receptor (CaSR) from vascular smooth muscle cells implicates the CaSR in vascular pathophysiology

Bone ◽  
2012 ◽  
Vol 51 (6) ◽  
pp. S24
Author(s):  
M. Schepelmann ◽  
T. Davies ◽  
P. Yarova ◽  
S. Brennan ◽  
W. Chang ◽  
...  
2008 ◽  
Vol 81 (2) ◽  
pp. 260-268 ◽  
Author(s):  
Masih-ul Alam ◽  
John Paul Kirton ◽  
Fiona L. Wilkinson ◽  
Emily Towers ◽  
Smeeta Sinha ◽  
...  

2017 ◽  
Vol 35 (3) ◽  
pp. 523-532 ◽  
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Ioana Alesutan ◽  
Rashad Tuffaha ◽  
Tilman Auer ◽  
Martina Feger ◽  
Burkert Pieske ◽  
...  

2009 ◽  
Vol 297 (3) ◽  
pp. R723-R728 ◽  
Author(s):  
Lauren G. VanLandingham ◽  
Kimberly P. Gannon ◽  
Heather A. Drummond

Recent studies suggest certain epithelial Na+channel (ENaC) proteins may be components of mechanosensitive ion channel complexes in vascular smooth muscle cells that contribute to pressure-induced constriction in middle cerebral arteries (MCA). However, the role of a specific ENaC protein, βENaC, in pressure-induced constriction of MCAs has not been determined. The goal of this study was to determine whether pressure-induced constriction in the MCA is altered in a mouse model with reduced levels of βENaC. Using quantitative immunofluorescence, we found whole cell βENaC labeling in cerebral vascular smooth muscle cells (VSMCs) was suppressed 46% in βENaC homozygous mutant (m/m) mice compared with wild-type littermates (+/+). MCAs from βENaC +/+ and m/m mice were isolated and placed in a vessel chamber for myographic analysis. Arteries from βENaC+/+ mice constricted to stepwise increases in perfusion pressure and developed maximal tone of 10 ± 2% at 90 mmHg ( n = 5). In contrast, MCAs from βENaC m/m mice developed significantly less tone (4 ± 1% at 90 mmHg, n = 5). Vasoconstrictor responses to KCl (4–80 mM) were identical between genotypes and responses to phenylephrine (10−7-10−4M) were marginally altered, suggesting that reduced levels of VSMC βENaC specifically inhibit pressure-induced constriction. Our findings indicate βENaC is required for normal pressure-induced constriction in the MCA and provide further support for the hypothesis that βENaC proteins are components of a mechanosensor in VSMCs.


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