In:
European Journal of Heart Failure, Wiley, Vol. 17, No. 5 ( 2015-05), p. 475-483
Abstract:
The release of the B‐type natriuretic peptide ( BNP ) is increased in heart failure ( HF ), a condition associated with oxidative stress. BNP is known to exert anti‐inflammatory effects including suppression of neutrophil superoxide ( O 2 − ) release. However, BNP ‐based restoration of homeostasis in HF is inadequate, and the equivocal clinical benefit of a recombinant BNP , nesiritide, raises the possibility of attenuated response to BNP . We therefore tested the hypothesis that BNP ‐induced suppression of neutrophil O 2 − generation is impaired in patients with acute HF . Methods and results We have recently characterized suppression of neutrophil O 2 − generation ( PMA ‐ or fMLP ‐stimulated neutrophil burst) by BNP as a measure of its physiological activity. In the present study, BNP response was compared in neutrophils of healthy subjects ( n = 29) and HF patients ( n = 45). Effects of BNP on fMLP ‐induced phosphorylation of the NAD (P)H oxidase subunit p47phox were also evaluated. In acute HF patients, the suppressing effect of BNP (1 µmol/L) on O 2 − generation was attenuated relative to that in healthy subjects ( P 〈 0.05 for both PMA and fMLP ). Analogously, BNP inhibited p47phox phosphorylation in healthy subjects but not in HF patients ( P 〈 0.05). However, O 2 − ‐suppressing effects of the cell‐permeable cGMP analogue (8‐ pCPT‐cGMP ) were preserved in acute HF . Conventional HF treatment for 5 weeks partially restored neutrophil BNP responsiveness ( n = 25, P 〈 0.05), despite no significant decrease in plasma NT‐proBNP levels. Conclusions BNP inhibits neutrophil O 2 − generation by suppressing NAD (P)H oxidase assembly. This effect is impaired in acute HF patients, with partial recovery during treatment.
Type of Medium:
Online Resource
ISSN:
1388-9842
,
1879-0844
DOI:
10.1002/ejhf.2015.17.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
1500332-2
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