Endogenous Endothelins Mediate Increased Acidification in Remnant Kidneys

Abstract

Abstract. 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 μEq/d, P = 0.4), but Nx animals exhibited greater in situ HCO3- 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 ETA/B receptor antagonist, decreased urinary net acid excretion in Nx animals (to 394 ± 99 μEq/d, P < 0.04 versus without bosentan); the decrease was mediated by decreased HCO3- 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 μM/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.