Cardiovascular characterization of the effect of the silencing of the electroneutral sodium/bicarbonate cotransporter (NBCn1)

GALLO D; DI MATTÍA RA; CIARROCCHI S; BLANCO PG; PORTIANSKY EL; ORLOWSKI A; AIELLO EA

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

“Cardiovascular characterization of the effect of the silencing of the electroneutral sodium/bicarbonate cotransporter (NBCn1)”Gallo Delfina1, Di Mattia Romina1, Ciarrocchi Sofía1, Blanco Paula2, Portiansky Enrique3, Orlowski Alejandro1, Aiello E. Alejandro1.1Centro de Investigaciones Cardiovasculares “Dr. Horacio Cingolani”, Facultad de Ciencias Médicas, Universidad Nacional de La Plata-CONICET. La Plata, Argentina.2Servicio de Cardiología, Facultad de Veterinaria, Universidad Nacional de La Plata. La Plata, Argentina.3Laboratorio de Análisis de Imágenes, Facultad de Veterinaria, Universidad Nacional de La Plata-CONICET. La Plata, Argentina.Cardiac cells depend on specific sarcolemmal ion transporters to assure the correct intracellular pH regulation. The Na+/HCO3- cotransporter (NBC) is one of the mayor alkalinizing transporters. In the heart, two different NBC isoforms have been described: the electroneutral NBCn1 (1Na+:1HCO3-) and the electrogenic NBCe1 (1Na+:2HCO3-). Preliminary results from our lab demonstrated that specific cardiovascular downregulation of NBCe1 induced cardiac hypertrophy (CH) without changes in blood pressure (BP). However, no clear reports about the role of the NBCn1 in these cardiovascular parameters are available. Thus, we developed an interference RNA cloned in a cardiotropic adeno-associated vector (AAV9-shNBCn1) to study the effect of the specific inhibition of NBCn1 in CH and BP. We delivered the virus through a lateral tail vein injection in male 3-4 months old Wistar rats and then performed a series of studies to assess CH, using an AAV9-shControl as control. Data is expressed as means±S.E.M. and is compared with Student's t-test or two-way ANOVA test as needed. After 30 days of injection, we confirm a significant reduction on NBCn1 ventricular expression in Wistar rats. Furthermore, preliminary data suggest a compensatory increase in NBCe1 expression. Although rats injected with shNBCn1 exhibited a significant increase in systolic blood pressure (shControl: 132.1±3.65, n=6; shNBCn1*: 151.2±4.29, n=4; p