Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats

Do Whan Ahn, Jin Mo Chung, Jee Yeun Kim, Kyoung Ryong Kim, Yang Saeng Park

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Chronic exposure to cadmium (Cd) results in bicarbonaturia, leading to metabolic acidosis. To elucidate the mechanism(s) by which renal bicarbonate reabsorption is inhibited, we investigated changes in renal transporters and enzymes associated with bicarbonate reabsorption in Cd-intoxicated rats. Cd intoxication was induced by subcutaneous injections of CdCl2 (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in Vmax of Na+/H+ antiport with no changes in KNa in the renal cortical brush-border membrane vesicles (BBMV). Western blotting of BBM proteins and indirect immunohistochemistry in renal tissue sections, using an antibody against Na+/H+ exchange-3 (NHE3), showed a diminished expression of NHE3 protein in the BBM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that NHE3 mRNA expression was reduced in the renal cortex. The activity of carbonic anhydrase IV (CA IV) in BBM was not changed. The protein abundance of Na +-HCO3- cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na +-K+-ATPase α-subunit was markedly elevated in Cd-intoxicated animals. These results indicate that Cd intoxication impairs NHE3 expression in the proximal tubule, thereby reducing the capacity for bicarbonate reabsorption, leading to bicarbonaturia in an intact animal.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalToxicology and Applied Pharmacology
Issue number1
StatePublished - Apr 1 2005
Externally publishedYes


  • Cadmium
  • Carbonic anhydrase
  • Kidney
  • Na /HCO cotransporter
  • Na/H exchanger

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology


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