Introduction of metoprolol increases plasma B-type cardiac natriuretic peptides in mild, stable heart failure.
BACKGROUND
The effect of beta-blockade on the cardiac natriuretic peptides is poorly understood but could contribute to their beneficial treatment effect and may be relevant to clinical use of plasma brain natriuretic peptide (BNP)/N-terminal pro brain natriuretic peptide (NTproBNP) measurements in risk stratification and in titration of anti-heart failure therapy.


RESULTS
Sixteen men with mild, stable heart failure (NYHA class II to III; left ventricular ejection fraction <40%) underwent serial blood sampling for plasma natriuretic peptide levels and received infusions of atrial natriuretic peptide (ANP) and BNP before and 6 weeks after the introduction and uptitration of metoprolol or 6 weeks unchanged therapy in a randomized, parallel-group design. Plasma natriuretic peptides (BNP, NTproBNP, ANP, and NTproANP) were increased by metoprolol (P<0.01 for all). The natriuretic responses to ANP and BNP infusions were sustained with the introduction of metoprolol despite reduced renal perfusion pressure. The levels of the noninfused natriuretic peptide were increased by both ANP and BNP infusions, and this effect was enhanced by metoprolol. The early plasma half-life (t(1/2)alpha) of BNP was prolonged by metoprolol (5.6+/-0.45 to 11+/-1.3 versus 5.7+/-0.8 to 6.6+/-1.3 minutes in control subjects; P=0.019).


CONCLUSIONS
Plasma cardiac natriuretic peptide levels increase significantly with the introduction of metoprolol in heart failure as a result of effects on secretion and clearance. Natriuretic responses to NP infusions are sustained with beta-blockade despite reduced renal perfusion pressure. Clinicians should be aware that the introduction of metoprolol causes a rise in plasma BNP/NTproBNP that is unrelated to deterioration in clinical status and must be considered when measurements are undertaken for risk stratification or titration of treatment.
Davis
Mark E
ME
The Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand. mark.davis@chmeds.ac.nz
Richards
A Mark
AM
Nicholls
M Gary
MG
Yandle
Timothy G
TG
Frampton
Christopher M
CM
Troughton
Richard W
RW
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D006152:Cyclic GMP / Q000652:urine; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000097:blood / Q000187:drug effects* / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D008790:Metoprolol; D006152:Cyclic GMP