Reactive oxygen species as second messengers of angiotensin II and aldosterone in the heart

AIELLO EA

Santiago de Chile

Congreso; Reunión Anual de la International Society for Heart Research (ISHR), sección Latinoamericana.; 2012

ISHR

During many years the reactive oxygen species (ROS) were exclusively considered as deleterious agents. However, over the last few years, many evidences supported the idea that ROS can also act as second messengers, mediating several intracellular signalling pathways. Consistently, we proposed the participation of these oxidative agents as mediators of certain cardiac physiological effects of angiotensin II (Ang II) and aldosterone. These effects are produced by the stimulation of the so called mechanism “ROS-induced-ROS release”, by which mitochondrial ROS are released to the citosol after the activation of the mitochondrial ATP-dependent K+ channels by ROS produced by the NADPH oxidase. We have proposed that these mitochondrial ROS stimulates the MAP kinase ERK, which in turn activates the Na+/H+ exchanger (NHE-1), inducing an increase in intracellular Na+([Na+]i). This [Na+]i enhancement promotes the increase in intracellular Ca2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.“ROS-induced-ROS release”, by which mitochondrial ROS are released to the citosol after the activation of the mitochondrial ATP-dependent K+ channels by ROS produced by the NADPH oxidase. We have proposed that these mitochondrial ROS stimulates the MAP kinase ERK, which in turn activates the Na+/H+ exchanger (NHE-1), inducing an increase in intracellular Na+([Na+]i). This [Na+]i enhancement promotes the increase in intracellular Ca2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.”, by which mitochondrial ROS are released to the citosol after the activation of the mitochondrial ATP-dependent K+ channels by ROS produced by the NADPH oxidase. We have proposed that these mitochondrial ROS stimulates the MAP kinase ERK, which in turn activates the Na+/H+ exchanger (NHE-1), inducing an increase in intracellular Na+([Na+]i). This [Na+]i enhancement promotes the increase in intracellular Ca2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.+ channels by ROS produced by the NADPH oxidase. We have proposed that these mitochondrial ROS stimulates the MAP kinase ERK, which in turn activates the Na+/H+ exchanger (NHE-1), inducing an increase in intracellular Na+([Na+]i). This [Na+]i enhancement promotes the increase in intracellular Ca2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.+/H+ exchanger (NHE-1), inducing an increase in intracellular Na+([Na+]i). This [Na+]i enhancement promotes the increase in intracellular Ca2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.+([Na+]i). This [Na+]i enhancement promotes the increase in intracellular Ca2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.2+ ([Ca2+]i) via the reverse mode of the Na+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.+/Ca2+ exchanger (NCX), leading to a positive inotropic effect. This increase in [Ca2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.2+]i could also trigger the development of cardiac hypertrophy by the calcineurin pathway. In addition, we have recently demonstrated that mitochondrial ROS are also able to stimulate the Na+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.+/HCO3− cotransport (NBC), a mechanism that, together with the NHE-1, regulates cardiac intracellular pH and [Na+] i by promoting the co-influx of Na+ and HCO3− into the cell.+] i by promoting the co-influx of Na+ and HCO3− into the cell.flux of Na+ and HCO3− into the cell.