Endogenous endothelins mediate increased acidification in remnant kidneys.
Because endothelins (ET) mediate increased renal acidification induced by dietary acid and animals with reduced renal mass exhibit increased urinary ET-1 excretion, the hypothesis that ET mediate increased renal acidification in remnant kidneys was tested. Four weeks before the study, rats underwent a 5/6 nephrectomy (Nx) and a microdialysis apparatus was inserted into the remnant left kidney and the left kidney of sham-treated control animals, for measurements of renal ET-1 contents. Nx animals exhibited greater ET-1 addition to the renal dialysate than did control animals (681 +/- 91 versus 290 +/- 39 fmol/g kidney wt per min, P < 0.002) and greater urinary ET-1 excretion (346 +/- 79 versus 125 +/- 24 fmol/d, P < 0.02). Urinary net acid excretion rates were similar for Nx and control animals (732 +/- 106 versus 1005 +/- 293 microEq/d, P = 0.4), but Nx animals exhibited greater in situ HCO(3)(-) reabsorption in proximal (972.3 +/- 77 versus 482.6 +/- 42.4 pmol/min, P < 0.001) and distal (62.7 +/- 6.7 versus 24.3 +/- 2.5 pmol/min, P < 0.001) tubules. Orally administered bosentan, an ET(A/B) receptor antagonist, decreased urinary net acid excretion in Nx animals (to 394 +/- 99 microEq/d, P < 0.04 versus without bosentan); the decrease was mediated by decreased HCO(3)(-) reabsorption in both the proximal and distal tubules. Furthermore, bosentan decreased blood base excess in Nx animals (0.1 +/- 0.3 to -0.12 +/- 0.03 microM/ml blood, P < 0.002), consistent with acid retention. The data demonstrate that endogenous ET mediate increased urinary acid excretion in the remnant kidneys of Nx animals.
Wesson
Donald E
DE
Texas Tech University Health Sciences Center, Texas Tech University School of Medicine, Lubbock, Texas.
D000042:Absorption; D000143:Acids / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000493:pharmacokinetics; D001682:Biological Availability; D001769:Blood / Q000378:metabolism; D000077300:Bosentan; D004231:Diuresis; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D005260:Female; D007668:Kidney / Q000378:metabolism* / Q000601:surgery*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D011184:Postoperative Period; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology; D015430:Weight Gain
D000143:Acids; D001639:Bicarbonates; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D000077300:Bosentan