title: Endothelin-induced increased aldosterone activity mediates augmented distal nephron acidification as a result of dietary protein.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Texas Tech University Health Sciences Center, Renal Section, 3601 Fourth Street, Lubbock, TX 79430, USA.
authors.forename: Apurv
authors.initials: A
authors.lastname: Khanna
authors.forename: Jan
authors.initials: J
authors.lastname: Simoni
authors.forename: Donald E
authors.initials: DE
authors.lastname: Wesson
mesh_terms: D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D000077300:Bosentan; D004044:Dietary Proteins / Q000494:pharmacology*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006863:Hydrogen-Ion Concentration; D007686:Kidney Tubules, Distal / Q000502:physiology*; D008297:Male; D006180:Proton-Translocating ATPases / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012076:Renal Agents / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D004044:Dietary Proteins; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D012076:Renal Agents; D013449:Sulfonamides; D000450:Aldosterone; D006180:Proton-Translocating ATPases; D000077300:Bosentan