CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Opposite effects of angiotensin II on Na+/HCO3- cotransporter isoforms: Role of ERK and p38 kinases
DE GIUSTI VC; AIELLO EA
Congreso; XX World Congress of the ISHR; 2010
Opposite effects of angiotensin II on Na+/HCO3- cotransporter isoforms: Role of ERK and p38 kinases Verónica C. De Giusti, Ernesto A. Aiello. Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP, La Plata, Argentina. The Na+/HCO3- cotransporter (NBC) is an important cardiac acid-extrusor. Electroneutral (NBCn; 1 Na+:1 HCO3-) and electrogenic (NBCe; 1 Na+:2 HCO3-) isoforms of NBC co-exist in the heart. We examined the role of ERK and p38 kinases as potential mediators of NBC regulation by 100 nM Angiotensin II (Ang II). Intracellular pH (pHi) was measured with epifluorescence in cat ventricular myocytes. Total NBC activity was evaluated during recovery from acidosis (NH4+ pulse, expressed as H+ flux, JH at pHi 6.8) and membrane depolarization with high extracellular K+ (K+ pulse, expressed as DpHi) was used to study NBCe in isolation. * indicates p<0.05 vs control. Ang II induced an increase in JH (1.70±0.15*, n=8 vs 1.03±0.12, n=11) that was prevented by the AT1 blocker losartan (10 µM; 0.93±0.20, n=6), the ERK inhibitor U0126 (10 µM; 0.56±0.18, n=6) and the reactive oxygen species (ROS) scavenger MPG (2 mM; 0.80±0.08, n=11). The K+ pulse produced a control pHi-enhancement (0.19±0.01, n=6) that was abolished by Ang II (-0.01±0.02*, n=5). This Ang II effect was prevented by losartan (0.19±0.02, n=4) or the p38 kinase inhibitor SB202190 (10 mM; 0.25±0.06, n=5), but was unaffected by U0126 (-0.07±0.04*, n=3) or MPG (-0.02±0.05*, n=8). The JH in the presence of both Ang II and SB202190 (2.15±0.07, n=5) was significantly greater than with Ang II alone. In conclusion, Ang II, binding to AT1 receptors, exerts opposite effects on NBC activity: stimulate NBCn in a ROS and ERK-dependent manner and inhibit NBCe through the p38 kinase pathway.