Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor

María C. Camilon de Hurtado, Irene L. Ennis, Néstor G. Pérez, Gladys E. Chiape de Cingolani, Patricio Morgan, Horacio E. Cingolani

Research output: Contribution to journalArticle

Abstract

Rats exposed to prolonged administration of the NHE-1 inhibitor cariporide showed enhanced activity of the exchanger in cardiac tissue, as assessed by the rise in the steady-state pHi value in the absence of bicarbonate (7.15 ± 0.01 in control vs 7.49 ± 0.06 and 7.41 ± 0.05 in cariporide-treated for 1 or 2 months, respectively, P <0.05). In the presence of bicarbonate, the change in pHi was blunted due to a compensatory activation of acid loading pHi regulatory mechanisms. The enhancement of NHE activity disappeared after 1 week of the inhibitor withdrawal. The kinetic analysis of H+ fluxes after an acid load revealed an increased net H+ efflux (JH+) ar any given pHi value and an alkaline shift of the apparent "set-point" of the exchanger (from 7.11 ± 0.02 to 7.38 ± 0.04, P <0.05) in treated rats. In the presence of the PKC inhibitor chelerythrine, the "set-point" of the exchanger was normalized in the cariporide-treated rats while JH+ at acidic pHi values persisted elevated. Cardiac NHE-1 mRNA levels and protein expression were increased in cariporide-treated rats. In addition to the increased protein expression after the treatment, the normalization of the augmented "set-point" by chelerythrine suggests an increased turnover rate of the units through a PKC dependent pathway. These data demonstrate that long-term treatment with the NHE-1 inhibitor cariporide enhances the antiporter activity in cardiac tissue through an increase of the number and turnover of functional units. This finding deserves further experimental and clinical evaluations to consider whether it would be advisable a gradual withdrawal of prolonged NHE inhibition to avoid an enhanced response when the exchanger is stimulated.

Original languageEnglish (US)
Pages (from-to)1539-1547
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume34
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Sodium-Hydrogen Antiporter
Up-Regulation
Bicarbonates
Antiporters
Acids
Proteins
cariporide
Messenger RNA

Keywords

  • Cariporide
  • Na/H exchanger
  • NHE-1 mRNA
  • Upregulation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Camilon de Hurtado, M. C., Ennis, I. L., Pérez, N. G., Chiape de Cingolani, G. E., Morgan, P., & Cingolani, H. E. (2002). Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor. Journal of Molecular and Cellular Cardiology, 34(11), 1539-1547. https://doi.org/10.1006/jmcc.2002.2107

Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor. / Camilon de Hurtado, María C.; Ennis, Irene L.; Pérez, Néstor G.; Chiape de Cingolani, Gladys E.; Morgan, Patricio; Cingolani, Horacio E.

In: Journal of Molecular and Cellular Cardiology, Vol. 34, No. 11, 01.11.2002, p. 1539-1547.

Research output: Contribution to journalArticle

Camilon de Hurtado, MC, Ennis, IL, Pérez, NG, Chiape de Cingolani, GE, Morgan, P & Cingolani, HE 2002, 'Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor', Journal of Molecular and Cellular Cardiology, vol. 34, no. 11, pp. 1539-1547. https://doi.org/10.1006/jmcc.2002.2107
Camilon de Hurtado MC, Ennis IL, Pérez NG, Chiape de Cingolani GE, Morgan P, Cingolani HE. Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor. Journal of Molecular and Cellular Cardiology. 2002 Nov 1;34(11):1539-1547. https://doi.org/10.1006/jmcc.2002.2107
Camilon de Hurtado, María C. ; Ennis, Irene L. ; Pérez, Néstor G. ; Chiape de Cingolani, Gladys E. ; Morgan, Patricio ; Cingolani, Horacio E. / Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor. In: Journal of Molecular and Cellular Cardiology. 2002 ; Vol. 34, No. 11. pp. 1539-1547.
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