Aldosterone Contributes to Vasopressin Escape through Changes in Water and Urea Transport

• Type of Material: Article
• Authors: Yanhua Wang, Emory University; Lauren M. LaRocque, Emory University; Joseph A. Ruiz, Emory University; Eva L. Rodriguez, Emory University; Jeff Sands, Emory University; Janet Klein, Emory University
• Language: English
• Date: 2023-07-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/biomedicines11071844
• Title of Journal or Parent Work: BIOMEDICINES
• Volume: 11
• Issue: 7
• Grant/Funding Information: This work was supported by an ASN Carl W. Gottschalk Research Scholar Grant to Y. Wang.
• Keywords: syndrome of inappropriate antidiuretic hormone secretion; Biochemistry & Molecular Biology; phosphatase; hyponatremia; Research & Experimental Medicine; Science & Technology; RECEPTOR; aldosterone; Pharmacology & Pharmacy; AQP2; COLLECTING DUCT; Medicine, Research & Experimental; BLOOD-PRESSURE; PHOSPHORYLATION; calcineurin; mineralocorticoid receptor; TRAFFICKING; ENAC; Life Sciences & Biomedicine
• Research Categories: Biology, Molecular; Chemistry, Biochemistry

Abstract

Hyponatremia (hypo-osmolality) is a disorder of water homeostasis due to abnormal renal diluting capacity. The body limits the degree to which serum sodium concentration falls through a mechanism called "vasopressin escape". Vasopressin escape is a process that prevents the continuous decrease in serum sodium concentration even under conditions of sustained high plasma vasopressin levels. Previous reports suggest that aldosterone may be involved in the vasopressin escape mechanism. The abilities of aldosterone synthase (Cyp11b2) knockout and wild-type mice to escape from vasopressin were compared. Wild-type mice escaped while the aldosterone synthase knockout mice did not. Both the water channel aquaporin 2 (AQP2) and the urea transporter UT-A1 protein abundances were higher in aldosterone synthase knockout than in wild-type mice at the end of the escape period. Vasopressin escape was also blunted in rats given spironolactone, a mineralocorticoid receptor blocker. Next, the role of the phosphatase, calcineurin (protein phosphatase 2B, PP2B), in vasopressin escape was studied since aldosterone activates calcineurin in rat cortical collecting ducts. Tacrolimus, a calcineurin inhibitor, blunted vasopressin escape in rats compared with the control rats, increased UT-A1, AQP2, and pS256-AQP2, and decreased pS261-AQP2 protein abundances. Our results indicate that aldosterone regulates vasopressin escape through calcineurin-mediated protein changes in UT-A1 and AQP2.