Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells

Abstract

This review is focused on the expression and regulation of amiloride-sensitive sodium channels in the epithelial cells of the aldosterone-sensitive distal nephron (ENaC) and amiloride-sensitive sodium channel activity in vascular endothelial and smooth muscle cells. Guyton’s hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. With the study of Mendelian forms of hypertension and their corresponding transgenic mouse models, the main components of the aldosterone- and angiotensin-dependent sodium transporters have been identified over the past 20 years. Proteolytic processing of the ENaC external domain, and inhibition by increased sodium concentrations are important features of the ENaC complexes expressed in the distal nephron. In contrast, amiloride-sensitive sodium channels expressed in the vascular system are activated by increased external sodium concentrations, resulting in changes in the mechanical properties and function of endothelial cells. Mechano-sensitivity and shear stress affect both epithelial and vascular sodium channel activity. The synergistic effects and complementary regulation of the epithelial and vascular systems are consistent with the Guytonian model of volume and blood pressure regulation, and may reflect sequential evolution of the two systems. The integration of vascular tone, renal perfusion and regulation of renal sodium reabsorption is the central underpinning of the Guytonian model. We summarize the recent evidence in this review that describes the central role of amiloride-sensitive sodium channels in the efferent (e.g., vascular) and afferent (e.g., epithelial) arms of this homeostatic system.

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

“…In the retinal choroid vascular bed, the activity of the KCa2.3 K + channel is requisite for the vasodilatory effect of aldosterone . The epithelial sodium channel (ENaC) is also modulated by aldosterone via MR in the endothelium (Kusche-Vihrog et al, 2008;Warnock et al, 2014). Because endothelial ENaC contributes to the stiffening The Mineralocorticoid Receptor in Pathology of endothelial cell membranes (Jeggle et al, 2013) and to the activity of eNOS (Perez et al, 2009), aldosterone/ MR modulation of endothelial ENaC expression/ activity is an important issue .…”

Endothelial Sodium Channels Trigger Endothelial Salt Sensitivity With Aging

“…8 The epithelial sodium channel is also expressed in vascular endothelium and has been termed endothelial sodium channel (EnNaC). 9 As in epithelia, synthesis and activation of EnNaC is regulated by the mineralocorticoid hormone aldosterone. 10 Specific EnNaC blockade completely prevents sodium-induced stiffening.…”

Recharging Red Blood Cell Surface by Hemodialysis

“…Although this change in plasma sodium is quite small it still may have considerable impact on vascular function. It has been shown that such a small change in plasma sodium stiffens vascular endothelial cells leading to endothelial dysfunction [12,13,14]. The only other significant change was found in the acid-base status (pCO 2 ) of patients with high salt sensitivity indicating a mild metabolic acidosis, compensated by hyperventilation.…”

“…Most likely this is caused by a mechanical interaction between RBC and vessel wall due to insufficient repulsive forces between the erythrocytes and the endothelial cell surface [8]. In the early days of hemodialysis mechanical destruction of erythrocytes during frequent hemodialysis was thought to be a major cause for anemia observed in these patients [7,8,9,10,11,12,13,14,15,16,17,18]. Along with the technical improvement of the dialysis equipment the adverse (mechanical) influence of the dialysis process by itself on erythrocyte survival became less [19,20].…”