Endogenous endothelins mediate increased distal tubule acidification induced by dietary acid in rats

J Clin Invest. 1997 May 1;99(9):2203-11. doi: 10.1172/JCI119393.

Abstract

We examined if endogenous endothelins mediate the decreased HCO3 secretion and increased H+ secretion in in vivo-perfused distal tubules of rats fed dietary acid as (NH4)2SO4. Animals given (NH4)2SO4 drinking solution had higher endothelin-1 addition to renal interstitial fluid than those given distilled H2O (480+/-51 vs. 293+/-32 fmol g kidney wt(-1) min(-1), respectively, P < 0.03). (NH4)2SO4-ingesting animals infused with bosentan (10 mg/kg) to inhibit A- and B-type endothelin receptors had higher HCO3 secretion than baseline (NH4)2SO4 animals (-4.7+/-0.4 vs. -2.4+/-0.3 pmol mm(-1) min(-1), P < 0.01), but (NH4)2SO4 animals given a specific inhibitor of A-type endothelin receptors (BQ-123) did not (-2.0+/-0.2 pmol mm(-1) min(-1), P = NS vs. baseline). H+ secretion was lower in bosentan-infused compared with baseline (NH4)2SO4 animals (27.7+/-2.5 vs. 43.9+/-4.0 pmol mm(-1) min(-1), P < 0.03), but that for BQ-123-infused (NH4)2SO4 animals was not (42.9+/-4.2 pmol mm(-1) min(-1), P = NS vs. baseline). Bosentan had no effect on distal tubule HCO3 or H+ secretion in control animals. The data show that dietary acid increases endothelin-1 addition to renal interstitial fluid and that inhibition of B- but not A-type endothelin receptors blunts the decreased HCO3 secretion and increased H+ secretion in the distal tubule of animals given dietary acid. The data are consistent with endogenous endothelins as mediators of increased distal tubule acidification induced by dietary acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acidosis, Renal Tubular / metabolism*
  • Ammonium Sulfate / pharmacology
  • Animals
  • Bicarbonates / metabolism*
  • Bosentan
  • Diet
  • Endothelin Receptor Antagonists
  • Endothelin-1 / metabolism*
  • Extracellular Space / metabolism
  • Female
  • Kidney Tubules, Distal / blood supply
  • Kidney Tubules, Distal / metabolism*
  • Male
  • Peptides, Cyclic / pharmacology
  • Protons
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology

Substances

  • Bicarbonates
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Peptides, Cyclic
  • Protons
  • Sulfonamides
  • Bosentan
  • cyclo(Trp-Asp-Pro-Val-Leu)
  • Ammonium Sulfate