| First Author | VanLandingham LG | Year | 2009 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 297 |
| Issue | 3 | Pages | R723-8 |
| PubMed ID | 19553501 | Mgi Jnum | J:152198 |
| Mgi Id | MGI:4356406 | Doi | 10.1152/ajpregu.00212.2009 |
| Citation | VanLandingham LG, et al. (2009) Pressure-induced constriction is inhibited in a mouse model of reduced betaENaC. Am J Physiol Regul Integr Comp Physiol 297(3):R723-8 |
| abstractText | 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. |
