Aldosterone mediates the cardiac sodium/bicarbonate (NBC) activation through a non-genomic and ROS-dependent mechanism

ORLOWSKI A; CIANCIO MC; DE GIUSTI VC; AIELLO EA

Congreso; XXI World Congress of the international society of heart research; 2013

ISHR

Aldosterone mediates the cardiac sodium/bicarbonate (NBC) activation through a non-genomic and ROS-dependent mechanism. Orlowski A, Ciancio MC, De Giusti VC, Aiello EA. Centro de Investigaciones Cardiovasculares. Fac. Cs. Médicas. UNLP-CONICET. La Plata, Argentina. The Na+/HCO3- cotransporter (NBC) regulates cardiac intracelular pH (pHi). In myocardium, aldosterone (Ald) increases the production of reactive oxygen species (ROS) and mediates the activation of CaMKII, leading to left ventricular hypertrophy. The aim of this study was to investigate the modulation of NBC by Ald. pHi was monitored using fluorescence measurements of BCECF in rat ventricular myocytes. The transport activity of NBC was evaluated during recovery from acidosis with an ammonium pulse (data expressed as percentage increase in HCO3- influx). * indicates p<0.05. Ald induced an increase of the total NBC activity of 44±11 %* (n=8), that was prevented by the mineralocorticoid receptor (MR) blocker eplerenone (1 µM, -3±9 %, n=4), the ROS scavenger MPG (2 mM, -0.2±12 %, n=4) and the NADPH oxidase inhibitor apocynin (300 µM, 8±12 %, n=4), but not by the protein synthesis blocker cycloheximide (10 µM, 36%±9 %*, n=4) or the CaMKII inhibitor KN93 (2.5 µM, 63±9 %*, n=6). Surprisingly, the estrogen G protein-couple receptor (GPR30) blocker G15 abolished the effect of Ald on NBC (1 µM, -8.5±3 %, n=5). Moreover, the GPR30 agonist G1 also activated NBC (1 µM, 57±17 %*, n=7) and this effect was prevented by G15 (1 µM, 1±10 %, n=5), eplerenone (1 µM, 14±9 %, n=6) and MPG (2 mM, -29±9 %, n=7). In conclusion, we demonstrated for first time the non-genomic stimulatory effect of Ald on cardiac NBC. Ald, acting on GPR30 (either directly or after MR binding), stimulates cardiac NBC in a ROS-dependent and CaMKII-independent manner. Since this transporter promotes Na+ influx to the cardiomyocyte, its stimulation could participate in the hypertrophic effect of Ald on the heart.