La angiotensina II activa al cotransportador Na+/HCO3- card¨ªaco por medio de las Especies Reactivas del Ox¨ªgeno y la v¨ªa de ERK.

DE GIUSTI VC; AIELLO EA

Buenos Aires, Argentina

Congreso; XV Congreso Argentino de Hipertension Arterial; 2008

Sociedad Argentina de Hipertensi¨®n

Angiotensin II stimulates the Na+/HCO3- cotransporter via generation of reactive oxygen species and stimulation of the ERK pathway. De Giusti VC, Aiello EA. Centro de Investigaciones Cardiovasculares; Fac. de Cs. M¨¦dicas, UNLP, La Plata, Argentina. The control of intracellular pH (pHi) is essential for cardiac activity. The major transporters responsible for acid extrusion are the Na+/H+ antiporter (NHE) and the Na+/HCO3- cotransporter (NBC). The latter promotes the co-influx of HCO3- and Na+ into the cell. The aim of the present investigation was to determinate the relative importance of the NBC in pHi recovery and elucidate if the reactive oxygen species (ROS) generated by Angiotensin (Ang II) result in ERK activation and NBC stimulation.  Intracellular pH was measured in isolated cat ventricular myocytes in a medium with bicarbonate using the fluorescent pH indicator BCECF. The NH4+ method was used to induce an intracellular acid load and the acid efflux (JH) was calculated as an indicator of NBC activity. JH was studied at a pHi of 6.8. The JH total was 3.19¡À0.35 mM/min; n=7. In the presence of HOE 642 10 ¦ÌM, NHE inhibitor, the JH was 1.06¡À0.15 mM/min, n=9; p<0.05 (JH control). With HOE 642, the addition of either SITS 0.1 mM or SO859 10 ¦ÌM (NBC blockers) abolished the recovery. The addition of Ang II 100 nM to the extracellular medium increased significantly the JH control (1.70¡À0.18 mM/min, n=6; p<0.05). The pre-treatment of cells with either MPG 2 mM, ROS scavenger, or U0126 10 ¦ÌM, MAP kinase ERK inhibitor, totally prevented the stimulatory effect of Ang II on the JH (0.83¡À0.09 mM/min, n=9, p<0.05, and 0.73¡À0.15 nM/min, n=5, p<0.05, respectively). These data indicate that the NBC participates in pHi recovery, being the only active mechanism when the NHE is blocked. Furthermore, we demonstrated that Ang II-induced stimulation of NBC activity requires increment of ROS production and activation of the ERK pathway, likely representing an important pathophysiologic mechanism under situations in which Ang II is elevated.