Liu, S., Ngo, D., Chong, C., Amarasekera, A., Procter, N., Licari, G., Dautov, R., Stewart, S., Chirkov, Y. & Horowitz, J. (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. Retrieved from https://doi.org/10.1002/ejhf.242
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.
Mary MacKillop Institute for Health Research