CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Angiotensin II inhibits the electrogenic Na+/HCO3- cotransporter (eNBC) in cat ventricular myocytes.
DE GIUSTI VC; AIELLO EA
Congreso; XVII Meeting ISHR Latin American Section.; 2009
Angiotensin II inhibits the electrogenic Na+/HCO3- cotransporter (eNBC) in cat ventricular myocytes. De Giusti VC, Aiello EA. Centro de Invest. Cardiovasc. (CIC). UNLP. In cardiomyocytes exist, at least, two isoforms of the NBC, one electroneutral (nNBC) and one electrogenic (eNBC). We have demonstrated that the eNBC produces an anionic repolarizing current which contributes with 25% of the normal duration of the cardiac action potential (DCAP). It is known that Angiotensin II (Ang II) increases the DCAP, leading to a potential arrhythmogenic state. In the present work we studied the effect of Ang II (100 nM) on the eNBC activity using cat myocytes and epifluorescence microscopy . We induce a membrane potential depolarization by increasing extracellular K+ [K+]o from 4.5 to 45mM which enhanced the driving force of eNBC (K+ pulse). The data are expressed as increase of pHi units after 14 minutes of applying the K+ pulse; * indicates statistically significant difference (Student test). The K+ pulse induced an increase of pHi of 0.19±0.008* (n=6) which was not affected by the specfic NHE inhibitor HOE642 (10 ìM, 0.185±0.039*; n=4) but was blunted by the NBC blocker SO589 (10 ìM, -0.004±0.016; n=5), indicating that this protocol is appropriate to study the eNBC.The pre-treatment of the cells with Ang II totally prevented the hyperkalemia-induced increase of pHi (-0.008±0.018, n=5) and this was inhibited by the addition of the AT1 receptor blocker losartan (1 ìM, 0.187±0.02*, n=4;). These results allow us to conclude that Ang II, binding to AT1 receptors, inhibits the eNBC, effect that may contribute to the detrimental prolongation of the DCAP induced by the hormone.