Mitochondrial reactive oxygen species (ROS) as signaling molecules of intracellular pathways triggered by the cardiac renin-angiotensin II-aldosterone system (RAAS).

Mitochondria represent major sources of basal reactive oxygen species (ROS) production of the cardiomyocyte. The role of ROS as signaling molecules that mediate different intracellular pathways has gained increasing interest among physiologists in the last years. In our lab, we have been studying the participation of mitochondrial ROS in the intracellular pathways triggered by the renin-angiotensin II-aldosterone system (RAAS) in the myocardium during the past few years. We have demonstrated that acute activation of cardiac RAAS induces mitochondrial ATP-dependent potassium channel (mitoKATP) opening with the consequent enhanced production of mitochondrial ROS. These oxidant molecules, in turn, activate membrane transporters, as sodium/hydrogen exchanger (NHE-1) and sodium/bicarbonate cotransporter (NBC) via the stimulation of the ROS-sensitive MAPK cascade. The stimulation of such effectors leads to an increase in cardiac contractility. In addition, it is feasible to suggest that a sustained enhanced production of mitochondrial ROS induced by chronic cardiac RAAS, and hence, chronic NHE-1 and NBC stimulation, would also result in the development of cardiac hypertrophy.

Mecanismo de acción de los antidepresivos: una mirada histórica / Mechanism of action of antidepressants: a historical look

En la década del 60, se asumía que la depresión consistía en una deficiencia de catecolaminas (hipótesis catecolaminérgica) y que los antidepresivos tricíclicos actuaban sobre ellas (principalmente noradrenalina) incrementándolas o potenciándolas a nivel central. Otras teorías sobre las bases biológicas de la depresión y el mecanismo de acción de los antidepresivos fueron planteadas posteriormente a medida que se daban evidencias sobre la participación de otros neurotransmisores. En la actualidad, se asume que el tipo de neurotransmisor implicado no es tan importante como los sistemas intraneuronales de traducción y transcripción de señales activados por la acción de los antidepresivos y que permiten estimular los mecanismos homeostáticos alterados de las neuronas disfuncionales, produciendo adaptaciones terapéuticas que llevan a alteraciones sustanciales y duraderas en la función neurona I y por lo tanto, a un nuevo estado funcional...

In the decade of6Os, were assumed that the depression was consistíng of a deficiency of catecholamines (catecholaminergic hypothesis) and that the trícyclic antidepressants were acting on them (mainly norepinephrine) increasing them at central level. Other theories on the biológical bases of depression and the actíon mechanism of antidepressants were outlined later while were given evidence on the participation of others eurotransmitters. Atpresent, itis assumed that the type of neurotransmitter involved is not so important as the intraneuronal systems ofsigns translation and transcription activated by the action of antidepressants and that permit to stimuíate homeostatic mechanisms alterad of disfunctional neurons, producing therapeutic adjustments that carry to substantial and lasting alterations in the neuronal function and there fore, to a new functíonal state...