Endogenous endothelins mediate increased acidification in remnant kidneys

Because endothelins (ET) mediate increased renal acidification induced by d ietary acid and animals with reduced renal mass exhibit increased urinary E T-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. f or measurements of renal ET-1 contents. Nx animals exhibited greater ET-1 a ddition 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 excr etion (346<plus/minus>79 versus 125 +/- 24 fmol/d. P<0.02). Urinary net aci d excretion rates were similar for Nx and control animals (732<plus/minus>1 06 versus 1005 +/- 293 mu Eq/d. P=0.4), but Nx animals exhibited greater in situ HCO3- reabsorption in proximal (972.3 +/- 77 versus 482.6 +/- 42.4 pm ol/min, P<0.001) and distal (62.7<plus/minus>6.7 versus 24.3 +/-2.5 pmol/mi n. P<0.001) tubules. Orally administered bosentan, an ETA/B receptor antago nist, decreased urinary net acid excretion in Nx animals (to 394<plus/minus >99 mu Eq/d, P<0.04 versus without bosentan); the decrease was mediated by decreased HCO3- reabsorption in both the proximal and distal tubules. Furth ermore, bosentan decreased blood base excess in Nx animals (0.1 +/-0.3 to - 0.12 +/-0.03 muM/ml blood, P<0.002). consistent with acid retention. The da ta demonstrate that endogenous ET mediate increased urinary acid excretion in the remnant kidneys of Nx animals.