[Beta-blockers in the treatment of cardiac insufficiency. Pharmacological bases].

Failure of the myocardial pump and poor adjustment of the cardiac output to the oxygen needs of the body, cause sympathetic reflexes (tachycardia and muscular, cutaneous, splanchnic and renal vasoconstriction) which concur to increase arterial blood pressure and cardiac output. This sympathetic hyperstimulation during the evolution of cardiac insufficiency results in many myocardial consequences: increase of the post-charge and cardiac work, depletion of the stock of neuromediator (nor-epinephrine) in the nerve endings of the myocardial sympathetic fibers and decrease of the number of beta-adrenergic receptors of the myocardial cell membranes. It is well known, now, that the "down-regulation" of beta-receptors involves, at least for a short time, a process of internalization of the receptors when subjected to intense stimulation by agonists receptors. A cell enzyme, the "beta-adrenergic receptor kinase" (BARK) causes a phosphorylation of certain sites of the proteins of the beta-receptor when stimulated by agonists. The receptor is then internalized in the cell and fails to be stimulated. It will become functional again and accessible under the membrane under the effect of another enzyme, a phosphatase. These pharmacological findings have led cardiologists to propose a beta-blocking treatment in severe forms (stage IV) of cardiac insufficiency. Biopsies of the myocardium in patients awaiting a heart transplant, have shown recently that under beta-blockers, the number of beta-functional receptors increased and this was interpreted as a response of myocardial cells to the blocking of remaining receptors (equivalent to an up-regulation phenomenon). This mechanism has been advocated to explain the excellent results of the treatment in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)