title: Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells.
abstract: Sodium transport in the distal nephron is mediated by epithelial sodium channel activity. Proteolytic processing of external domains and inhibition with increased sodium concentrations are important regulatory features of epithelial sodium channel complexes expressed in the distal nephron. By contrast, sodium channels expressed in the vascular system are activated by increased external sodium concentrations, which results in changes in the mechanical properties and function of endothelial cells. Mechanosensitivity and shear stress affect both epithelial and vascular sodium channel activity. Guyton's hypothesis stated that blood pressure control is critically dependent on vascular tone and fluid handling by the kidney. 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 probably 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. In this Review, we focus on the expression and regulation of sodium channels, and we outline the emerging evidence that describes the central role of amiloride-sensitive sodium channels in the efferent (vascular) and afferent (epithelial) arms of this homeostatic system.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 34294-0007, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.affiliation: Institut für Physiologie II, Westfälische Wilhelms Universität, Robert-Koch-Straße 27, 48149 Münster, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
authors.affiliation: INSERM U872 Team 1, Centre de Recherche des Cordeliers, Université René Descartes, Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Tarjus
authors.affiliation: Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Shaohu
authors.initials: S
authors.lastname: Sheng
authors.affiliation: Institut für Physiologie II, Westfälische Wilhelms Universität, Robert-Koch-Straße 27, 48149 Münster, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.affiliation: Renal and Electrolyte Division, Department of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kleyman
authors.affiliation: INSERM U872 Team 1, Centre de Recherche des Cordeliers, Université René Descartes, Université Pierre et Marie Curie, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Jaisser
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009399:Nephrons / Q000378:metabolism*
chemical_list: D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D000584:Amiloride