Neurohumoral activation is characteristic in patients with chronic heart failure (CHF). Furthermore, patients with the highest level of plasma norepinephrine (a general marker for neurohumoral activation) have the poorest survival profiles after a diagnosis of CHF. Great strides have been made in the treatment of CHF over the past two decades. ß Adrenergic receptor blockade and angiotensin-converting enzyme inhibition have become the gold standard for treatment of patients with CHF. Certainly, older pharmacological therapies are also still being used. These include diuretics and positive inotropes. In addition to these therapies, newer agents such as angiotensin receptor blockers, aldosterone antagonists, and endothelin-1 antagonists have had some success in reducing the mortality and morbidity associated with CHF. The reduction in neurohumoral drive that accompanies these therapies also has resulted in improved survival for patients with CHF. However, the mortality rate from this disease remains unacceptably high. Over the past decade, small clinical trials evaluating the role of exercise training as a treatment method for patients with CHF have been carried out and are well summarized by Piña et al.(7).

Although some studies, such as those by Belardinelli et al.(1), have shown clinical benefit of long-term supervised exercise training of patients with CHF, the precise mechanisms responsible for enhanced survival are not known. As shown in Table 1, most of the known mediators of neurohumoral function are activated in the CHF state. Therapeutic benefit largely has been attributed to inhibition of one or more of these mediators. In this review, we summarize some of the recent data from our laboratories implicating changes in the neurohormonal control of circulation after exercise training in experimental CHF.