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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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 (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.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalEuropean Journal of Heart Failure
Volume17
Issue number5
DOIs
Publication statusPublished - 1 May 2015
Externally publishedYes

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Keywords

  • Acute heart failure
  • BNP
  • Redox stress
  • Superoxide

Cite this

Liu, S., Ngo, D. T. M., Chong, C. R., Amarasekera, A. T., Procter, N. E. K., Licari, G., Dautov, R. F., Stewart, S., Chirkov, Y. Y., & Horowitz, J. D. (2015). Suppression of neutrophil superoxide generation by BNP is attenuated in acute heart failure: A case for 'BNP resistance'. European Journal of Heart Failure, 17(5), 475-483. https://doi.org/10.1002/ejhf.242