The epithelial sodium channel (ENaC): Mediator of the aldosterone response in the vascular endothelium?
In the kidney the epithelial sodium channel (ENaC) is regulated by the mineralocorticoid hormone aldosterone, which is essential for long-term blood pressure control. Evidence has accumulated showing that ENaC is expressed in endothelial cells. Moreover, its activity modifies the biomechanical properties of the endothelium. Therefore, the vascular system is also an important target for aldosterone and responds to the hormone with an increase in cell volume, surface area, and mechanical stiffness. These changes occur in a concerted fashion from minutes to hours and can be prevented by the specific sodium channel blocker amiloride and the mineralocorticoid receptor (MR) blocker spironolactone. Aldosterone acts on cells of the vascular system via genomic and non-genomic pathways. There is evidence that the classical cytosolic MR could mediate both types of response. Using a nanosensor covalently linked to aldosterone, binding sites at the plasma membrane were identified by atomic force microscopy. The interaction of aldosterone and this newly identified surface receptor could precede the slow classic genomic aldosterone response resulting in fast activation of endothelial ENaC. Recent data suggest that aldosterone-induced ENaC activation initiates a sequence of cellular events leading to a reduced release of vasodilating nitric oxide. We propose a model in which ENaC is the key mediator of aldosterone-dependent blood pressure control in the vascular endothelium.
Kusche-Vihrog
Kristina
K
Institute of Physiology II, University of Muenster, Muenster, Germany. kusche@uni-muenster.de
Callies
Chiara
C
Fels
Johannes
J
Oberleithner
Hans
H
D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000584:Amiloride