Neurohumoral activation in congestive heart failure

This article reviews the evidence that congestive heart failure is accompanied by an increased plasma norepinephrine concentration and that this is due not only to a reduced tissue clearance of the substance but also to a marked increase in sympathetic nerve activity. It also reports data that indicate that the sympathetic activation is associated with an activation of the renin-angiotensin system and an increased plasma level of vasopressin. At which degree of congestive heart failure these phenomena become manifest is not clear, but some studies suggest that the sympathetic and renin-angiotensin systems may be normal in asymptomatic congestive heart failure but already somewhat activated when this condition reaches New York Heart Association class II. There is also evidence that this activation, though initially compensatory, is eventually responsible for a number of adverse cardiovascular effects that account for the negative relationship between this event and survival. Finally, the article discusses the inability of the increased plasma level of atrial natriuretic peptide that characterizes congestive heart failure to offset the adverse effects of the neurohumoral activation and the variable influence of drug treatment on this phenomenon. This is not impossible to achieve, however, because heart transplantation appears to rapidly normalize a major factor in the increased sympathetic activity observed before surgical intervention, that is, impairment of the arterial baroreflex.