The specific inhibition of the cardiac electrogenic sodium/bicarbonate cotransporter (NBCe1) leads to cardiac hypertrophy

DI MATTÍA RA; JAQUENOD DE GIUSTI C; BLANCO P; PORTIANSKY E; AIELLO EA; ORLOWSKI A

Rosario

Congreso; Reunión anual de la Sociedad Argentina de Fisiología (SAFIS); 2019

SAFIS

Introduction: The Na+/HCO3- cotransporter (NBC) is one of the main alkalinizing transporters on cardiomyocytes. There are two isoforms of NBC: the electrogenic NBCe1 (2 HCO3-: 1 Na+) and the electroneutral NBCn1 (1 HCO3-: 1 Na+). Although both isoforms enters Na+ into the cell, NBCe1 contributes with half of Na+ per HCO3-, therefore it has a major efficiency. We have previously found in cardiac hypertrophy (CH) models that there was a reduction of NBCe1 activity together with an increased NBCn1 activity. However, we were unable to demonstrate the exact cause-consequence involvement of these NBC isoforms in the development of CH. Experimental design: We developed an interference RNA cloned in an adeno-associated vector (AAV9-siNBCe1) to study the effect of the specific inhibition of NBCe1 in CH. We delivered the virus through a lateral tail vein injection in male 3 months old Wistar rats and then performed a series of studies to assess CH, using an AAV9-siControl as control. Both vectors also contained GFP.Results: After 30 days of injection, euthanasia was performed. We first made sure that cardiomyocytes were green on a confocal microscopy and that we had a significance reduction on NBCe1 expression in the heart, by western blotting. In addition, we compared the left ventricle mass index (LVMI) obtained by echocardiography. We found an increase of LVMI in hearts injected with the siNBCe1 (siControl: 0.99±0.09, n=8; siNBCe1*: 1.55±0.16, n=6; *p