ISSN: 2329-9495
Panayotis Fantidis, Eladio Sanchez, Ijaz Khan, Ibrahim Tarhini, Tomás Pineda, José Antonio Corrales and José Ramón Gonzalez
Heart failure, characterized by the reduction in left and /or right ventricular function, is the most common cause of mortality and morbidity in almost around the world. This syndrome is induced by β1-adrenergic receptor (β1-AR) desensitization, which in turn is caused by the reduction in cellular cAMP concentration. Cellular cAMP concentration is modulated by adenylyl cyclases (ACs), a family of enzymes that are strongly activated by intracellular magnesium and circulating levels of the stress-related hormones. Short-term activation of β1-AR signalling pathway by increased levels of these hormones induces an increase in intracellular Mg2+ and cAMP concentrations, which improves cardiac function. Nevertheless, long-term activation of β1-AR signalling pathway by elevated levels of these hormones reduces intracellular Mg2+ and cAMP levels, which deteriorates cardiac function. Intracellular cAMP signalling has a circadian rhythm (CR) in mammals, and CR may modulate diverse phenomena. The loss of CR may per se be a cause of severe diseases. Magnesium can regulate intracellular cAMP production and through this may modulate the CR. Here we propose that longterm activation of β1-AR signalling pathway, and /or the use of diuretics, can induce a progressive reduction of intracellular of magnesium and a subsequent gradual reduction of intracellular cAMP levels. This in turn can cause β1-AR desensitization, the loss of CR of the hormones related with HF, and, finally, HF development. We suggest the therapeutic implications of this mechanism in the prevention of HF.