Dietary salt enhances benzamil-sensitive component of myogenic constriction in mesenteric arteries

Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H409-20. doi: 10.1152/ajpheart.00571.2007. Epub 2007 Nov 16.

Abstract

Recent work from our laboratory indicates that epithelial Na(+) channel (ENaC) function plays an important role in modulating myogenic vascular reactivity. Increases in dietary sodium are known to affect vascular reactivity. Although previous studies have demonstrated that dietary salt intake regulates ENaC expression and activity in epithelial tissue, the importance of dietary salt on ENaC expression in vascular smooth muscle cells (VSMCs) and its role in myogenic constriction is unknown. Therefore, the goal of the present study was to determine whether dietary salt modulates ENaC expression and function in myogenic vasoconstriction. To accomplish this goal, we examined ENaC expression in freshly dispersed VSMCs and pressure-induced vasoconstrictor responses in isolated mesenteric resistance arteries from normotensive Sprague-Dawley rats fed a normal-salt (NS; 0.4% NaCl) or high-salt (HS; 8% NaCl for 2 wk) diet. VSMCs from the mesenteric arteries of NS-fed animals express alpha-, beta-, and gamma-ENaC. The HS diet reduced whole cell alpha- and gamma-ENaC and induced a pronounced translocation of beta-ENaC from intracellular regions toward the VSMC membrane (approximately 336 nm). Associated with this change in expression was a change in the importance of ENaC in pressure-induced constriction. Pressure-induced constriction in NS-fed animals was insensitive to ENaC inhibition with 1 microM benzamil, suggesting that ENaC proteins do not contribute to myogenic constriction in mesenteric arteries under NS intake. In contrast, ENaC inhibition blocked pressure-induced constriction in HS-fed animals. These data suggest that dietary sodium regulates ENaC expression and the quantitative importance of the vascular ENaC signaling pathway contributing to myogenic constriction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Epithelial Sodium Channel Blockers*
  • Epithelial Sodium Channels / metabolism
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / metabolism
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Phenylephrine / pharmacology
  • Potassium Chloride / pharmacology
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers / pharmacology*
  • Sodium Chloride, Dietary / administration & dosage
  • Sodium Chloride, Dietary / pharmacology*
  • Time Factors
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology

Substances

  • Epithelial Sodium Channel Blockers
  • Epithelial Sodium Channels
  • Scnn1a protein, rat
  • Scnn1b protein, rat
  • Scnn1g protein, rat
  • Sodium Channel Blockers
  • Sodium Chloride, Dietary
  • Vasoconstrictor Agents
  • benzamil
  • Phenylephrine
  • Potassium Chloride
  • Amiloride