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.

Variability of NT-proBNP plasma and urine levels in patients with stable heart failure: a 2-year follow-up study

“…Some studies show a decrease in plasma BNP levels in patients who receive treatment with spironolactone 31 or with furosemide. 32 Furthermore, one study concludes that renal excretion of NT-proBNP is modified by enalapril, 33 but it remains to be determined if this is a direct effect of ACE-I. Thus, in order to extrapolate our results, sample collection during a follow-up study should be carried out in a stable therapeutic setting similar to that presented in our work.…”

Characterization of NT-proBNP in Human Urine

“…Urine NT-proBNP immunoreactivity has been determined in physiological studies (9,10 ), in heart failure (11)(12)(13)(14), for screening of left ventricular dysfunction in the community (15 ), and for prediction of cardiovascular events in heart failure (16 ). These studies and an editorial (17 ) suggest that urine NT-proBNP represents an alternative to plasma NT-proBNP as a clinical biomarker.…”