The effects of angiotensin-converting enzyme inhibition on the urinary excretion of NTproBNP in male volunteers.
OBJECTIVE
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.
Heringlake
Matthias
M
Department of Anesthesiology, University of Lübeck, Lübeck, Germany. heringlake@t-online.de
Will
Barbara
B
Klaus
Stephan
S
Heinze
Hermann
H
Wagner
Klaus
K
Pagel
Horst
H
Wergeland
Ragnhild
R
Bahlmann
Ludger
L
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D006400:Hematocrit; D006728:Hormones / Q000097:blood; D006801:Humans; D007677:Kidney Function Tests; D049449:Luminescence; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000652:urine*; D010446:Peptide Fragments / Q000097:blood / Q000652:urine*; D012964:Sodium / Q000652:urine; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D006728:Hormones; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D004656:Enalapril; D012964:Sodium