Altered Tissue Degradation and Distribution of Atrial Natriuretic Peptide in Patients With Idiopathic Dilated Cardiomyopathy and Its Relationship With Clinical Severity of the Disease and Sodium Handling

Abstract

Background Atrial natriuretic peptide (ANP) has been suggested to play an important role in heart failure, preserving cardiorenal homeostasis through maintenance of the sodium balance and inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether there is a disturbed renewal and distribution of ANP in patients with idiopathic dilated cardiomyopathy (IDC) with differing clinical severity of disease. Methods and Results We used a tracer method to perform a cross-sectional study of 15 IDC patients with differing clinical severity (New York Heart Association functional class I to III), prospectively divided into two groups according to their functional class (group 1, classes I and II; group 2, classes II-III and III). Eleven normotensive, nonobese male volunteers also were studied as a control group. Main ANP kinetic parameters were derived from the disappearance curve of the labeled hormone after the bolus injection of [ 125 I]-labeled ANP. A high-performance liquid chromatography technique was used to separate the radiolabeled hormone in each plasma sample. Patients in group 1 showed higher ANP metabolic clearance rate (MCR) (2731.9±726.2 mL · min −1 · m −2 ) than patients of group 2 (1718.4±621.2 mL · min −1 · m −2 ) and control subjects (1873.1±551.2 mL · min −1 · m −2 ). ANP disposal (MCR) positively correlated with biological hormonal effect (urinary sodium excretion) both in control subjects and in patients. In IDC patients of both groups, however, MCR values were always higher (approximately doubled) than the values found in control subjects at the corresponding sodium excretion. This finding indicates that a reduced ANP biological activity is associated with hormone degradation in patients. Moreover, patients of group 2 showed significantly higher ANP production rates (395.6±183.8 ng · min −1 · m −2 ) than group 1 (166.0±139.0 ng · min −1 · m −2 ) and control subjects (130.7±105.4 ng · min −1 · m −2 ) despite a marked reduction in sodium excretion. Patients with IDC showed a progressive reduction in the total distribution volume (group 1, 19.8±5.8 L/m 2 ; group 2, 12.7±6.9 L/m 2 ; control subjects, 27.0±11.6 L/m 2 ) of the hormone; this probably was due to a reduction in exchanges of ANP with peripheral tissues. Conclusions Our study demonstrates a markedly altered degradation and distribution of ANP in patients with IDC, even in those at the early stage of clinical disease (classes I and II, group 1) who have ANP plasma levels in the normal range.