title: Pressure-induced constriction is inhibited in a mouse model of reduced betaENaC.
abstract: 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, betaENaC, 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 betaENaC. Using quantitative immunofluorescence, we found whole cell betaENaC labeling in cerebral vascular smooth muscle cells (VSMCs) was suppressed 46% in betaENaC homozygous mutant (m/m) mice compared with wild-type littermates (+/+). MCAs from betaENaC +/+ and m/m mice were isolated and placed in a vessel chamber for myographic analysis. Arteries from betaENaC+/+ mice constricted to stepwise increases in perfusion pressure and developed maximal tone of 10 +/- 2% at 90 mmHg (n = 5). In contrast, MCAs from betaENaC 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 betaENaC specifically inhibit pressure-induced constriction. Our findings indicate betaENaC is required for normal pressure-induced constriction in the MCA and provide further support for the hypothesis that betaENaC proteins are components of a mechanosensor in VSMCs.
authors: Dept. of Physiology and Biophysics, Univ. of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, USA.
authors: Lauren G
authors: LG
authors: VanLandingham
authors: Kimberly P
authors: KP
authors: Gannon
authors: Heather A
authors: HA
authors: Drummond
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D020768:Middle Cerebral Artery / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D053503:Epithelial Sodium Channels; C507049:Scnn1b protein, mouse; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride