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Endothelin-Induced Increased Aldosterone Activity Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein

Apurv Khanna^*, Jan Simoni and Donald E. Wesson^*,

Departments of ^* Internal Medicine, Surgery, and Physiology, Texas Tech University Health Sciences Center, Texas Tech University School of Medicine, Lubbock, Texas

Address correspondence to: Dr. Donald E. Wesson, Texas Tech University Health Sciences Center, Renal Section, 3601 Fourth Street, Lubbock, TX 79430. Phone: 806-743-3107; Fax: 806-743-3177; E-mail: donald.wesson{at}ttuhsc.edu

Received for publication December 7, 2004. Accepted for publication March 22, 2005.

The hypothesis that increased dietary protein augments distal nephron acidification through endothelin-mediated increased aldosterone activity was tested. Munich-Wistar rats were studied after 3 wk of diets with 50% high protein (HiPro) and 20% control (CON) casein-provided protein, the latter comparable to standard diet. HiPro versus CON rats had higher distal nephron H⁺ secretion by in vivo microperfusion as shown previously. Perfusion with inhibitors of Na⁺/H⁺ exchange (EIPA, 10^–5 M), H⁺-ATPase (bafilomycin, 10^–7 M), and H⁺-K⁺-ATPase (Sch 28080 [10^–5 M] and ouabain [10^–3 M]) support that higher Na⁺/H⁺ exchange and higher H⁺-ATPase but not higher H⁺-K⁺-ATPase activity mediated increased H⁺ secretion in HiPro rats. Oral bosentan, an endothelin A/B receptor antagonist, decreased distal nephron H⁺ secretion in HiPro rats as a result of reduced Na⁺/H⁺ exchange and H⁺-ATPase activity as shown previously by the authors’ laboratory. HiPro versus CON rats had higher plasma aldosterone (60.9 ± 5.9 versus 42.2 ± 4.4 pg/ml; P < 0.024) and higher urine aldosterone excretion (21.9 ± 3.9 versus 10.5 ± 2.8 ng/d; P < 0.04) in the absence but not presence of bosentan, consistent with endothelin-mediated increased aldosterone secretion. HiPro rats that did versus did not ingest the aldosterone antagonist spironolactone had lower distal nephron H⁺ secretion (29.2 ± 3.3 versus 42.1 ± 3.8 pmol/mm per min; P < 0.05) as a result of lower H⁺-ATPase activity without differences in Na⁺/H⁺ exchange or H⁺-K⁺-ATPase activity. The data support that dietary protein provided as casein increases distal nephron acidification through endothelin-stimulated Na⁺/H⁺ exchange and endothelin-stimulated aldosterone secretion that increases H⁺-ATPase activity.

This article has been cited by other articles:

				D. E. Wesson, J. Simoni, and S. Prabhakar Endothelin-Induced Increased Nitric Oxide Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein J. Am. Soc. Nephrol., February 1, 2006; 17(2): 406 - 413. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673