Suppression of neutrophil superoxide generation by BNP is attenuated in acute heart failure: a case for `BNP resistance'

Saifei Liu, Doan T. M. Ngo, Cher-Rin Chong, Anjalee T. Amarasekera, Nathan E. K. Procter, Giovanni Licari, Rustem F. Dautov, Simon Stewart, Yuliy Y. Chirkov, John D. Horowitz

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7 Citations (Scopus)

Abstract

Aims: 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 (O2−) 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 O2− generation is impaired in patients with acute HF. Methods and results: We have recently characterized suppression of neutrophil O2− 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 O2− 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, O2−‐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 O2− generation by suppressing NAD(P)H oxidase assembly. This effect is impaired in acute HF patients, with partial recovery during treatment.
Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalEuropean Journal of Heart Failure
Volume17
Issue number5
Early online date11 Feb 2015
DOIs
Publication statusPublished - 1 May 2015

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