Present and future trends in research and clinical applications of inodilators

The rationale of combining vasodilatation with positive inotropic intervention in the treatment of chronic heart failure has found a new implementation in the "inodilator" drugs. Inodilators are characterized by the properties of exerting positive inotropic effect and inducing systemic vasodilatation. The cellular mechanisms involved in the regulation of contractility of cardiac and vascular muscle and the pathophysiological events occurring in heart failure are briefly discussed, and the pharmacological profile as well as the therapeutic use of these drugs are reviewed. On the basis of the mechanism of action, two groups of inodilators are distinguished, the phosphodiesterase inhibitors and the dopaminergic agents. The increase of [cAMP]i induced by the phosphodiesterase inhibitors is responsible for their vasodilating effect and for the positive inotropic action, but many of them have in addition the ability to enhance the Ca2+ sensitivity of cardiac contractile proteins. The complex organization and the cardinal role of the catecholaminergic receptor system in the control of cardiovascular function and its contribution to the pathophysiological events occurring in heart failure are the rational basis of the therapeutic use of dopaminergic agents. These drugs, acting on DA, beta-, and alpha-receptors, exert not only positive inotropic and vasodilating effects, but also a diuretic action, and can reduce aldosterone and renin secretion, blunt an excessive sympathetic activity, and possibly promote the release of atrial natriuretic peptide. The multireceptor mechanism of dopamine-like drugs, which accounts for their favorable hemodynamic, neurohumoral, and diuretic effects, represents the most promising approach to inodilator therapy.