title: Endothelin-1 inhibits sodium reabsorption by ET(A) and ET(B) receptors in the mouse cortical collecting duct.
abstract: The collecting duct (CD) is a major renal site for the hormonal regulation of Na homeostasis and is critical for systemic arterial blood pressure control. Our previous studies demonstrated that the endothelin-1 gene (edn1) is an early response gene to the action of aldosterone. Because aldosterone and endothelin-1 (ET-1) have opposing actions on Na reabsorption (JNa) in the kidney, we postulated that stimulation of ET-1 by aldosterone acts as a negative feedback mechanism, acting locally within the CD. Aldosterone is known to increase JNa in the CD, in part, by stimulating the epithelial Na channel (ENaC). In contrast, ET-1 increases Na and water excretion through its binding to receptors in the CD. To date, direct measurement of the quantitative effect of ET-1 on transepithelial JNa in the isolated in vitro microperfused mouse CD has not been determined. We observed that the CD exhibits substantial JNa in male and female mice that is regulated, in part, by a benzamil-sensitive pathway, presumably ENaC. ENaC-mediated JNa is greater in the cortical CD (CCD) than in the outer medullary CD (OMCD); however, benzamil-insensitive JNa is present in the CCD and not in the OMCD. In the presence of ET-1, ENaC-mediated JNa is significantly inhibited. Blockade of either ETA or ETB receptor restored JNa to control rates; however, only ETA receptor blockade restored a benzamil-sensitive component of JNa. We conclude 1) Na reabsorption is mediated by ENaC in the CCD and OMCD and also by an ENaC-independent mechanism in the CCD; and 2) ET-1 inhibits JNa in the CCD through both ETA and ETB receptor-mediated pathways.
authors.affiliation: Research Service, North Florida/South Georgia Veterans Health System, 1601 SW Archer Road, Gainesville, FL 32608. cswingo@ufl.edu.
authors.forename: I Jeanette
authors.initials: IJ
authors.lastname: Lynch
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Welch
authors.forename: Donald E
authors.initials: DE
authors.lastname: Kohan
authors.forename: Brian D
authors.initials: BD
authors.lastname: Cain
authors.forename: Charles S
authors.initials: CS
authors.lastname: Wingo
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D044022:Receptor, Endothelin A / Q000378:metabolism*; D044023:Receptor, Endothelin B / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D053503:Epithelial Sodium Channels; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C013407:benzamil; D000584:Amiloride; D012964:Sodium
keywords: aldosterone; collecting duct; endothelin-1; kidney; mineralocorticoid; sodium reabsorption