4.6 Article

Regulation of Intracellular pH is Altered in Cardiac Myocytes of Ovariectomized Rats

Journal

Publisher

WILEY
DOI: 10.1161/JAHA.118.011066

Keywords

Alcalinizing transporters; cardiac myocyte; cardiac remodeling; cardiovascular pathophysiology

Funding

  1. Agencia Nacional de Promocion Cientifica y Tecnologica de Argentina (ANCPyT) [PICT 2014 2594, PICT 2016 2099]
  2. Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP 0664]

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Background-It is well known that after menopause women are exposed to a greater cardiovascular risk, but the intracellular modifications are not properly described. The sodium/proton exchanger (NHE) and the sodium/bicarbonate cotransporter (NBC) regulate the intracellular pH and, indirectly, the intracellular sodium concentration ([Na+]). There are 2 isoforms of NBC in the heart: the electrogenic (1Na(+)/2HCO(3)(-); NBCe1) and the electroneutral (1Na(+)/1HCO(3)(-); NBCn1). Because NHE and NBCn1 hyperactivity as well as the NBCe1 decreased activity have been associated with several cardiovascular pathologies, the aim of this study was to investigate the potential alterations of the alkalinizing transporters during the postmenopausal period. Methods and Results-Three-month ovariectomized rats (OVX) were used. The NHE activity and protein expression are significantly increased in OVX. The NBCe1 activity is diminished, and the NBCn1 activity becomes predominant in OVX rats. p-Akt levels showed a significant diminution in OVX. Finally, NHE activity in platelets from OVX rats is also higher in comparison to sham rats, resulting in a potential biomarker of cardiovascular diseases. Conclusions-Our results demonstrated for the first time that in the cardiac ventricular myocytes of OVX rats NHE and NBC isoforms are altered, probably because of the decreased level of p-Akt, compromising the ionic intracellular homeostasis.

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