Atrial natriuretic peptide and urinary cyclic guanosine monophosphate in patients with chronic heart failure

Abstract

Circulating concentrations of human atrial natriuretic peptide (hANP) are elevated in patients with heart failure; however, the natriuretic effect of hANP is blunted in these patients. In this study, the relationship between urinary cGMP, the second messenger for the natriuretic effect of hANP in vivo, and endogenous hANP was examined in six patients with heart failure and four normal subjects. In addition, right heart catheterization for the determination of central hemodynamics was performed in the heart failure patients. The heart failure patients were in New York Heart Association Classes II to IV and were receiving no medications at the time of the study. Supine plasma hANP and urinary cGMP concentrations were determined on two occasions in each subject, as were right and left atrial pressures in the heart failure patients. At the time of study, the patients were in positive sodium balance, and control subjects were in normal sodium balance. Plasma hANP and urinary cGMP excretion rates were elevated in heart failure patients as compared with those in controls: hANP, 139.0 ± 42.0 versus 22.0 ± 6.1 pg/mL (P < 0.05); urinary cGMP, 1.14 ± 0.31 versus 0.35 ± 0.05 nmol/ min (P < 0.05). In heart failure patients, right atrial pressure correlated positively with plasma hANP (r = 0.96; P < 0.01) and urinary cGMP concentrations (r = 0.93; P < 0.05) and the excretion rate (r = 0.92; P < 0.05). Moreover, plasma hANP was strongly correlated with urinary cGMP concentration (r = 0.91; P < 0.01). These results demonstrate that urinary cGMP is elevated in heart failure patients, strongly correlating with plasma hANP and atrial pressure, and support the active biological responsiveness of renal hANP receptors in heart failure patients.