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Vascular ENaC proteins are required for renal myogenic constriction

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

Submitted 19 January 2005 ; accepted in final form 20 May 2005

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 that DEG/ENaC proteins are required for myogenic constriction in renal vessels, we first determined expression of ENaC transcripts and proteins in mouse renal VSMCs. Then, we determined pressure- and agonist-induced constriction and changes in vascular smooth muscle 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 mouse renal VSMC. 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, abolishes pressure-induced constriction and increases in cytosolic Ca²⁺ and Na⁺ without diminishing agonist-induced responses in isolated mouse interlobar arteries. Our findings indicate that 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.

mechanotransduction; renal blood flow autoregulation; amiloride; benzamil; isolated renal vessel; stretch-activated cation channel; calcium; sodium

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