Na/H exchange and H-K ATPase increase distal tubule acidification in chronic alkalosis

Kidney International
D E Wesson

Abstract

We examined whether H(+)-ATPase, H(+)-K(+)-ATPase, and or Na+/H+ exchange mediates increased distal tubule acidification in animals with chronic metabolic alkalosis using pharmacological inhibitors of these H+ transporters in in vivo-perfused tubules of anesthetized rats. Chronic metabolic alkalosis was induced with furosemide followed by minimum electrolyte diet and HCO3 drinking water. The reduction in net HCO3 reabsorption was greater in distal tubules of alkalotic compared to control animals perfused with Schering 28080 to inhibit H(+)-K(+)-ATPase (-6.4 +/- 0.9 vs. -1.4 +/- 0.5 pmol/mm.min-1, P < 0.02) and with EIPA to inhibit Na+/H+ exchange (-11.1 +/- 1.7 vs. -6.6 +/- 0.9 pmol/mm.min-1, P < 0.01) but was similar in distal tubules of alkalotic and control animals perfused with bafilomycin to inhibit H(+)-ATPase. The greater reduction of distal tubule net HCO3 reabsorption in alkalotic compared to control animals induced by EIPA was eliminated by systemic infusion of the endothelin receptor antagonist bosentan (-4.6 +/- 0.7 vs. -4.4 +/- 0.7 pmol/mm.min-1, P = NS) but the greater reduction induced by Schering 28080 persisted. Urine endothelin-1 (ET-1) excretion was higher in animals with maintained alkalosis (164.5 +/- 23.7 ...Continue Reading

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Citations

Dec 6, 2001·Current Hypertension Reports·D E Wesson
Sep 2, 2004·Journal of the American Society of Nephrology : JASN·Apurv KhannaDonald E Wesson
Jun 10, 2011·American Journal of Physiology. Renal Physiology·Juan CodinaThomas D DuBose
Jul 31, 2009·American Journal of Physiology. Renal Physiology·Michelle L GumzCharles S Wingo
Oct 6, 2006·Kidney International·D E Wesson
May 6, 2005·Journal of the American Society of Nephrology : JASN·Apurv KhannaDonald E Wesson
Dec 18, 2004·The Journal of Physiology·Matthew A BaileyTong Wang
Oct 31, 2006·Seminars in Nephrology·Donald E Wesson
Aug 19, 2011·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·F John Gennari

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