title: Endothelial sodium channels trigger endothelial salt sensitivity with aging.
abstract: The epithelial sodium channel is also expressed in vascular endothelium (endothelial sodium channel [EnNaC]). Depending on ambient sodium concentration, EnNaC is associated with mechanical stiffening of the endothelial cell cortex, leading to endothelial dysfunction. Because the incidence of both salt sensitivity and endothelial dysfunction increases with age, we investigated the abundance of EnNaC in aging mice. To assess EnNaC functionality and endothelial salt sensitivity, stiffness was measured while ambient sodium was varied. Aortae of young (3 months) and old (15 months) C57BL/6J wild-type mice were kept ex vivo on a physiological concentration of aldosterone (0.45 nmol/L). Spironolactone (10 nmol/L) and amiloride (1 μmol/L) were applied for aldosterone antagonism and EnNaC blockage, respectively. EnNaC at the endothelial cell surface was quantified by immunofluorescence staining. Cortical stiffness was monitored by atomic force microscopy when ambient sodium was raised from 135 to 150 mmol/L. In ex vivo aortae of older mice, endothelial cells had significantly higher EnNaC numbers than those of younger mice (+23%). In parallel, cortical stiffness was found increased (+8.5%). Acute application of high sodium led to an immediate rise in stiffness in both groups but was pronounced in endothelium of older mice (+18% versus +26%). Spironolactone and amiloride lowered EnNaC abundance and prevented endothelial stiffening under all conditions. We conclude that EnNaC mediates endothelial salt sensitivity in the aging process. This mechanism might contribute to the development of age-related cardiovascular disease and suggests the usage of spironolactone and amiloride specifically in the elderly.
authors.affiliation: From the Institute of Physiology II (M.P., K.K.-V., V.D., H.O.) and Department of Internal Medicine D (H.P., K.K.), University Hospital of Münster, Münster, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Paar
authors.affiliation: From the Institute of Physiology II (M.P., K.K.-V., V.D., H.O.) and Department of Internal Medicine D (H.P., K.K.), University Hospital of Münster, Münster, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.affiliation: From the Institute of Physiology II (M.P., K.K.-V., V.D., H.O.) and Department of Internal Medicine D (H.P., K.K.), University Hospital of Münster, Münster, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
authors.affiliation: From the Institute of Physiology II (M.P., K.K.-V., V.D., H.O.) and Department of Internal Medicine D (H.P., K.K.), University Hospital of Münster, Münster, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Drüppel
authors.affiliation: From the Institute of Physiology II (M.P., K.K.-V., V.D., H.O.) and Department of Internal Medicine D (H.P., K.K.), University Hospital of Münster, Münster, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.affiliation: From the Institute of Physiology II (M.P., K.K.-V., V.D., H.O.) and Department of Internal Medicine D (H.P., K.K.), University Hospital of Münster, Münster, Germany. Katrin.Kliche@ukmuenster.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kliche
mesh_terms: D000375:Aging / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D051379:Mice; D012965:Sodium Chloride / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology; D059289:Vascular Stiffness / Q000187:drug effects / Q000502:physiology*
chemical_list: D053503:Epithelial Sodium Channels; D013148:Spironolactone; D012965:Sodium Chloride; D000584:Amiloride
keywords: aging; endothelium, vascular; sodium channels