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

Research output: Contribution to journalArticlepeer-review

13 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
DOIs
Publication statusPublished - 2015

Keywords

  • anti, inflammatory agents
  • heart failure
  • medical care
  • superoxides

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