Endogenous endothelins mediate increased distal tubule acidification induced by dietary acid in rats.
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.
Wesson
D E
DE
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock 79430, USA. phydew@ttuhsc.edu
D000141:Acidosis, Renal Tubular / Q000378:metabolism*; D000645:Ammonium Sulfate / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D000077300:Bosentan; D004032:Diet; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D007686:Kidney Tubules, Distal / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D001639:Bicarbonates; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D011522:Protons; D013449:Sulfonamides; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D000645:Ammonium Sulfate