Downregulation of cardiac NBCn1 isoform increases blood pressure in rats

DELFINA GALLO; ROMINA DI MATTÍA; SOFÍA CIARROCCHI; ENRINQUE PORTIANSKY; PAULA BLANCO; ALEJANDRO ORLOWSKI; ERNESTO ALEJANDRO AIELLO

La Plata, Buenos Aires

Congreso; 2022 Annual Meeting of ISHR Lat; 2022

International Society for Heart Research - Latinoamerican section

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 was compared with Student´s t-test or two-way ANOVA test as was 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