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1 Department of Physiology and Biophysics and the Center for Excellence in Caediovascular Renal Research, University of Mississippi Medical Center, Jackson, MS, USA
* To whom correspondence should be addressed. E-mail: hdrummond{at}physiology.umsmed.edu.
The myogenic response is an essential component of renal blood flow autoregulation and
is the inherent ability of vascular smooth muscle cells (VSMCs) to contract in response to
increases in intraluminal pressure. Although mechanosensitive ion channels are thought to
initiate VSMC stretch-induced contraction, their molecular identity is unknown. Recent reports
suggest Degenerin/Epithelial Na+ Channels (DEG/ENaC) may form mechanotransducers in
sensory neurons and VSMCs, however, the role of DEG/ENaC proteins in myogenic constriction
of mouse renal arteries has not been established. To test the hypothesis DEG/ENaC proteins are
required for myogenic constriction in renal vessels, we first determined expression of ENaC
transcripts and proteins in mouse renal VSMCs (mrVSMCs). Then, we determined pressure- and
agonist-induced constriction and changes in VSM cytosolic Ca2+ and Na+ in isolated mouse
renal interlobar arteries following DEG/ENaC inhibition with amiloride and benzamil. We
detect
-,
-, and
ENaC transcript and protein expression in cultured mrVSMC. In contrast, we
detect only
- and
-, but not
-, ENaC protein in freshly dispersed mrVMSC. Selective
DEG/ENaC inhibition, with low doses of amiloride and benzamil, abolish pressure-induced
constriction and increases in cytosolic Ca2+ and Na+ without diminishing agonist-induced
responses in isolated mouse interlobar arteries. Our findings indicate DEG/ENaC proteins are
required for myogenic constriction in mouse interlobar arteries and are consistent with our
hypothesis that DEG/ENaC proteins may be components of mechanosensitive ion channel
complexes required for myogenic vasoconstriction.
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