ATTENUATED RENAL EXCRETORY RESPONSE TO ATRIAL-NATRIURETIC-PEPTIDE IN CONGESTIVE-HEART-FAILURE IN MAN

The renal and hormonal effects of atrial natriuretic peptide given as a bolus injection (2.0-mu-g/kg) were studied in 12 patients with congestive heart failure before and after treatment with captopril for 4 weeks and in 13 healthy control subjects. Atrial natriuretic peptide caused a rise in urinary excretion of sodium and urinary flow in the controls, whereas no increases were observed in the patients. Both proximal and distal fractional reabsorption of sodium, as evaluated by the lithium clearance technique, decreased less in the patients than in the controls. Basal plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP), and the basal urinary excretion of cGMP, were elevated in the patients. The increases in both plasma and urinary cGMP after administration of atrial natriuretic peptide were blunted in heart failure. Basal glomerular filtration rate and renal plasma flow were reduced, and filtration fraction increased, in the patients. A positive correlation (r = 0.958, P < 0.01) was found between renal plasma flow and the relative increase in urinary excretion of sodium in the patients with heart failure. Treatment with captopril did not improve the natriuretic and diuretic effect of exogenous atrial natriuretic peptide, but resulted in an increase in filtration fraction after administration of atrial natriuretic peptide not present before captopril. It is concluded that the natriuretic and diuretic effect of exogenous atrial natriuretic peptide is blunted in congestive heart failure in man due to reduced responsiveness in both proximal and distal tubules. It is suggested that preoccupation/downregulation of the receptors for atrial natriuretic peptide rather than the reninangiotensin-aldosterone system, is involved in the pathogenesis of the attenuated renal response to exogenous atrial natriuretic peptide in congestive heart failure.