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

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.

Effects of amiloride, benzamil, and alterations in extracellular Na+ on the rat afferent arteriole and its myogenic response

“…More recently, the same laboratory found that the myogenic responses of the rat mesenteric resistance arteries are not attenuated by benzamil, unless animals were placed on a high-salt diet (18). The effects of amiloride on the mesenteric myogenic response were not reported in this latter study.…”

Renal Autoregulation in Health and Disease

“…Benzamil (1 M) inhibited the myogenic response only in arteries from rats fed a high-salt diet (730).…”

“…ENaC ␣-and ␥ -subunit expression in mesenteric arteries was reduced by high-salt diet, whereas ␤-ENaC movement to the plasma membrane of VSMCs was increased (730). Benzamil (1 M) inhibited the myogenic response only in arteries from rats fed a high-salt diet (730).…”

Amiloride lowers arterial pressure in cyp1a1ren-2 transgenic rats without affecting renal vascular function

“…Subunits of the renal epithelial sodium channel (ENaC) are expressed in many tissues including renal collecting duct, lung and colon epithelia [1] as well as endothelial and vascular smooth muscle cells [2][3][4][5]. ENaC expressed in the vascular wall may participate in the regulation of vascular tone under normal and pathological conditions.…”