PT  - JOURNAL ARTICLE
AU  - Khanna, Apurv
AU  - Simoni, Jan
AU  - Wesson, Donald E.
TI  - Endothelin-Induced Increased Aldosterone Activity Mediates Augmented Distal Nephron Acidification as a Result of Dietary Protein
AID  - 10.1681/ASN.2004121054
DP  - 2005 Jul 01
TA  - Journal of the American Society of Nephrology
PG  - 1929--1935
VI  - 16
IP  - 7
4099  - http://jasn.asnjournals.org/content/16/7/1929.short
4100  - http://jasn.asnjournals.org/content/16/7/1929.full
SO  - J. Am. Soc. Nephrol.2005 Jul 01; 16
AB  - 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.