Principles of therapy for congestive heart failure.

Vascular smooth muscle differs from myocardial tissue in several critical ways: (1) calcium ion entry is achieved by at least two channels; (2) both alpha-1 and alpha-2 postjunctional receptors regulate vascular tone; (3) calmodulin increases the activity of the myosin light chain kinase; (4) cyclic AMP decreases rather than increases cytosolic calcium ion concentration; (5) angiotensin increases vascular tone without a positive inotropic effect by acting on angiotensin receptors which ultimately increase vascular cytosolic calcium. Each of these factors allows for a specific therapeutic approach to the problem of congestive heart failure by altering vascular tone. Alternatively, positively inotropic interventions aim to increase the cytosolic calcium ion concentration in the myocardium. Besides the conventional approach by digitalis glycosides, beta-agonists and amrinone are also thought to increase the myocardial cytosolic calcium ion concentration. Hence many of the therapeutic approaches to congestive heart failure aim to reduce vascular smooth muscle calcium or to increase myocardial muscle cell calcium.