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

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 vs. 76.6 +/- 10.8 fmol/day, P < 0.03), but decreased following KCl repletion to a value (86.7 +/- 10.0 fmol/day, P < 0.02 vs. respective before-KCl value) that was not different from that for KCl-repleted control animals (79.9 +/- 8.7 fmol/day, P = NS vs. KCl-repleted alkalotic animals). The data support that augmented distal tubule acidification in alkalotic animals is due to increased H(+)-K(+)-ATPase and Na+/H+ exchange activity, the latter stimulated by endogenous endothelins.

• Authors: D E Wesson
• Journal: Kidney international (Kidney Int) Vol. 53 Issue 4 Pg. 945-51 (Apr 1998) ISSN: 0085-2538 [Print] United States
• PMID: 9551402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Acids
• Anti-Arrhythmia Agents
• Anti-Bacterial Agents
• Bicarbonates
• Endothelins
• Enzyme Inhibitors
• Imidazoles
• Macrolides
• Sodium-Hydrogen Exchangers
• Sch 28080
• bafilomycin A
• Aldosterone
• Amiloride
• H(+)-K(+)-Exchanging ATPase
• ethylisopropylamiloride

Topics

• Acid-Base Equilibrium (drug effects, physiology)
• Acids (urine)
• Aldosterone (blood)
• Alkalosis (metabolism)
• Amiloride (analogs & derivatives, pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Anti-Bacterial Agents (pharmacology)
• Bicarbonates (metabolism)
• Endothelins (urine)
• Enzyme Inhibitors (pharmacology)
• Female
• H(+)-K(+)-Exchanging ATPase (metabolism)
• Imidazoles (pharmacology)
• Kidney Tubules, Distal (enzymology)
• Macrolides
• Male
• Rats
• Rats, Wistar
• Sodium-Hydrogen Exchangers (metabolism)