The degree of activation of neurohormonal mechanisms appears to depend on the severity and acuteness of cardiac impairment as well as the status of the extracellular fluid volume. Vasoconstrictive antinatriuretic mechanisms are markedly activated in severe decompensated cardiac failure. These are accompanied by parallel increases in endogenous vasodilatory natriuretic activities that modulate the powerful vasoconstrictive mechanisms. During chronic compensation, many of these neuroendocrine mechanisms returned to the baseline normal level. In addition to endocrine and neurogenic mechanisms, local autocrine-paracrine systems in the blood vessel wall may also contribute to the regulation of vascular tone. The role of these systems in congestive heart failure has not been systematically studied. It is possible that they may contribute to the long-term regulation of vascular tone and therefore may play an increasing role in the pathogenesis of ventricular remodeling, dilatation and progressive congestive heart failure.