Department of Cardiology and Clinical Pharmacology, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of Adelaide, South Australia, Australia.
Eur J Heart Fail. 2015 May;17(5):475-83. doi: 10.1002/ejhf.242. Epub 2015 Feb 11.
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.
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.
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.
脑钠肽（BNP）在心力衰竭（HF）中释放增加，而心力衰竭与氧化应激有关。已知 BNP 具有抗炎作用，包括抑制中性粒细胞超氧化物（O2(-)）的释放。然而，基于 BNP 的 HF 体内平衡恢复是不足的，重组 BNP 奈西立肽的临床获益不确定，这增加了对 BNP 反应减弱的可能性。因此，我们检验了这样一个假设，即在急性 HF 患者中，BNP 诱导的中性粒细胞 O2(-)产生抑制作用受损。
我们最近将 BNP 抑制中性粒细胞 O2(-)产生（PMA 或 fMLP 刺激的中性粒细胞爆发）的作用作为其生理活性的指标进行了描述。在本研究中，我们比较了健康受试者（n=29）和 HF 患者（n=45）的中性粒细胞中 BNP 的反应。还评估了 BNP 对 NAD(P)H 氧化酶亚基 p47phox 磷酸化的影响。在急性 HF 患者中，与健康受试者相比，BNP（1µmol/L）对 O2(-)产生的抑制作用减弱（PMA 和 fMLP 均为 P<0.05）。类似地，BNP 抑制健康受试者的 p47phox 磷酸化，但不抑制 HF 患者的磷酸化（P<0.05）。然而，在急性 HF 中，细胞通透性 cGMP 类似物（8-pCPT-cGMP）的 O2(-)抑制作用得以保留。尽管血浆 NT-proBNP 水平没有显著降低，但常规 HF 治疗 5 周后部分恢复了中性粒细胞对 BNP 的反应性（n=25，P<0.05）。
BNP 通过抑制 NAD(P)H 氧化酶组装来抑制中性粒细胞 O2(-)的产生。在急性 HF 患者中，这种作用受损，在治疗过程中部分恢复。
