Deficiencies in activity of the
atrial natriuretic peptide (
ANP) system may be able to explain the disturbed
electrolyte and fluid homeostasis occurring in chronic
heart failure. Generally, in studies concerning the possible pathophysiologic role of
ANP in
heart failure, only the circulating levels of the
hormone were measured. It has been shown, however, that plasma
ANP levels exhibit marked variability attributable to the pulsatory pattern of secretion and to its very short plasma half-life. An evaluation of the main turnover parameters might represent a significant improvement in the assessment of the functioning of the overall
ANP system. By using a tracer method, which does not alter the steady-state condition, a disturbed peripheral metabolism of
ANP and a resistance to its
biologic effects was demonstrated in patients with
idiopathic dilated cardiomyopathy, even in those in the asymptomatic phase of the disease, showing
ANP circulating levels, atrial pressure and volume, and cardiac index within the normal range. The altered degradation and distribution of
ANP in patients with
heart failure were demonstrated by a great increase in metabolic clearance (on average, 2.5-fold), production (on average, 6-fold), or both, and by a progressive reduction in the distribution spaces of the
hormone when compared with normal subjects at the same
sodium intake. The ratio between
ANP disposal and the daily excretion of
sodium (equal to the
sodium intake in subjects at a strictly controlled
sodium balance) may give a good index of the
biologic activity (natriuresis) of the
ANP system. Preliminary studies suggest that an index of
biologic activity of the
ANP system may be a useful tool for the comparison of the efficacy of different therapeutic strategies in
heart failure. Indeed, after a 2-month treatment with an
angiotensin-converting enzyme inhibitor, this index was returned to within the normal range, suggesting that the
drug was able to "normalize" the peripheral distribution and degradation of the
hormone in these patients. Although future studies in a large series of patients will be useful to assess this important issue, the setup of accurate methods able to evaluate the presence and degree of resistance to
biologic activity of
ANP may be a useful tool in the follow-up evaluation of patients with
heart failure, and may pave the way for further progress in the knowledge of more general physiologic and pathophysiologic mechanisms of this important clinical condition.