Increased endothelin activity mediates augmented distal nephron acidification induced by dietary protein.
We tested the hypothesis that increased dietary protein augments distal nephron acidification through an endothelin-dependent mechanism. Munich-Wistar rats ate minimum electrolyte diets of 50% (HiPro) and 20% (CON) casein-provided protein, the latter comparable to standard chow. HiPro vs. CON had higher distal nephron H+ secretion (41.3 +/- 4.0 vs. 23.0 +/- 2.1 pmol/mm.min, p < 0.002) mediated by augmented Na+/H+ exchange and H(+)-ATPase activity. Renal cortex of HiPro vs. CON had higher ET-1 addition to microdialysate and higher ET-1 mRNA, consistent with increased renal ET-1 production. Bosentan, an endothelin A/B receptor antagonist, decreased HiPro distal nephron H+ secretion (28.4 +/- 2.4 vs. 41.3 +/- 4.0 pmol/mm.min, p < 0.016) through decreased Na+/H+ exchange and decreased H(+)-ATPase activity. Increased dietary protein augments distal nephron acidification through an endothelin-sensitive increase in Na+/H+ exchange and H(+)-ATPase activity, supporting an endothelin role in the distal nephron response to this common challenge to acid-base status.
Khanna
Apurv
A
Texas Tech University Health Sciences Center, Department of Internal Medicine, Texas Tech University School of Medicine, Lubbock, Texas 79430, USA.
Simoni
Jan
J
Hacker
Callenda
C
Duran
Marie-Josée
MJ
Wesson
Donald E
DE
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D000077300:Bosentan; D018076:DNA, Complementary / Q000235:genetics; D004044:Dietary Proteins / Q000008:administration & dosage*; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D018076:DNA, Complementary; D004044:Dietary Proteins; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D013449:Sulfonamides; D000077300:Bosentan