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

Liu, Saifei, Ngo, Doan T. M., Chong, Cher-Rin, Amarasekera, Anjalee T., Procter, Nathan E. K., Licari, Giovanni, Dautov, Rustem F., Stewart, Simon, Chirkov, Yuliy Y. and Horowitz, John 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). pp. 475-483. ISSN 1388-9842

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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 (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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 20 Nov 2018 09:30
Last Modified: 22 Apr 2020 07:14
URI: https://ueaeprints.uea.ac.uk/id/eprint/68977
DOI: 10.1002/ejhf.242

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