ROS signaling underlying the inotropic actions of angiotensin II and endothelin-1

AIELLO EA

Kyoto, Japón.

Conferencia; XX World Congress of the International Society for Heart Research (ISHR); 2010

International Society for Heart Research (ISHR)

ROS signaling underlying the inotropic actions of angiotensin II and endothelin-1. Ernesto Alejandro Aiello. Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, UNLP. La Plata. Argentina.   During many years reactive oxygen species (ROS) were considered deleterious agents, but in the last years many evidences of their effects as second messengers have emerged. Consistently, we have reported that ROS are the mediators of the cardiac inotropic response to angiotensin II or endothelin-1. These effects are due to the activation of the “ROS-induced ROS-release mechanism”, by which mitochondrial ROS are released to the cytosol after activation of the mitochondrial ATP sensitive K+ channel (mKATP) by ROS produced by the NADPH oxidase. We have also provided evidence that linked these mitochondrial ROS to the stimulation of the MAP kinase ERK, which in turn activates the Na+/H+ exchanger (NHE-1), causing an increment in the intracellular Na+ concentration ([Na+]i). This increase in [Na+]i promotes the increase in intracellular Ca2+ concentration ([Ca2+]i) through the reverse mode of the Na+/Ca2+ exchanger, leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger cardiac hypertrophy by activation of widely recognized Ca2+-dependent intracellular signaling pathways. Finally, we have recently reported that mitochondrial ROS produced by angiotensin II are also able to stimulate the Na+/HCO3- cotransport (NBC), which accelerates the recovery of cardiac intracellular pH during acidosis. The potential impact of this NBC stimulation on the increase in contractility induced by this hormone remains unknown.