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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/R723    most recent 00212.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by VanLandingham, L. G. Articles by Drummond, H. A. PubMed PubMed Citation Articles by VanLandingham, L. G. Articles by Drummond, H. A.

ARTICLES

Pressure-induced constriction is inhibited in a mouse model of reduced βENaC

Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi

Submitted 16 April 2009 ; accepted in final form 22 June 2009

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^–4 M) 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.

epithelial Na⁺ channel; ion channel; degenerin; myogenic constriction; middle cerebral artery