The Effects of Angiotensin-Converting Enzyme Inhibition on the Urinary Excretion of NTproBNP in Male Volunteers

Abstract

Aims: This study was designed to test if the renal excretion of the N-terminal prohormone of the B-type natriuretic peptide (NTproBNP) is modulated by angiotensin-converting enzyme inhibition (ACE-I). Methods: Following 7 days on a sodium-enriched diet and an induction period of 4 days with incremental dosages of enalapril (2.5, 5, 7.5, 10 mg) or placebo, 10 healthy subjects underwent crossover and double-blind treatment with 20 mg enalapril sodium or placebo at 8:00 h. After 4 h (at 12:00 h), 20 ml·kg^–1 NaCl 0.9% was infused over 60 min. Hemodynamics were determined and blood and urine were sampled at 8:00, 12:00, 13:00, 14:00, 16:00, and 18:00 h. Angiotensin II (AII), NTproANP, and NTproBNP were determined by radio- and electrochemiluminescence immunoassays. Results: In the whole group, ACE-I led to a lower arterial blood pressure during the fourth day of induction and during the time from 8:00 to 16:00 h, a decrease in AII levels from 8:00 to 14:00 h (p < 0.05), and to a higher cumulative urine output (p < 0.05) in comparison with control. Neither cumulative sodium nor urinary NTproBNP/creatinine excretion were significantly increased after ACE-I. However, a subgroup of 6 volunteers – showing an increase in sodium excretion after ACE-I – also demonstrated lower AII levels at 13:00 h, a higher cumulative urine flow, and a higher urinary NTproBNP/creatinine excretion in comparison with control (all: p < 0.05). Conclusions: This suggests that the renal excretion of NTproBNP is modified by enalapril. However, it remains to be determined if this is a direct effect of ACE-I, the decrease in arterial blood pressure, or other potentially confounding variables like bradykinin or endopeptidase activity.