Abstract 17067: Brain Natriuretic Peptide (BNP) Suppresses Neutrophil Superoxide Release: Attenuation in Patients with Congestive Heart Failure (CHF)
Background: The release of brain natriuretic peptide (BNP) in patients with congestive heart failure (CHF) has been presumed to serve a homeostatic function. However equivocal clinical benefit associated with BNP administration in CHF raises the possibility of attenuated response in such patients. In order to test this hypothesis we have evaluated the effects of BNP administration on cyclic guanosine monophosphate and superoxide release in normal subjects (n=15) compared with patients with CHF (n=15).
Methods: Neutrophils were isolated with a Ficoll gradient technique followed by lysis of red blood cells and resuspend in Hank’s Balanced Salt Solution with purity of >95% and viability of >98%. Neutrophils were incubated with BNP (1nM-1uM). Cyclic guanosine monophosphate generation was measured via radioimmunoassay while superoxide generation in response to phorbol 12-myristate 13-acetate (PMA) (100nM) was quantitated by electron paramagnetic resonance spectroscopy. Patients with CHF were largely extensively pretreated: 73% on angiotensin converting enzyme inhibitors/angiotensin II receptor blockers, 73% on β-adrenoceptor antagonists, and 53% on aldosterone antagonists.
Results: In neither normal nor CHF subjects did BNP significantly increase neutrophil cyclic guanosine monophosphate production ( In healthy subjects [-3.0±5.97%] [n=14]; in CHF [-12.52±9.83%] [n=5]). However, BNP reduced PMA-associated superoxide production in normal subjects in concentrations of 1nM (n=13) and 1uM (n=15). In patients with CHF (n=15), there was no change in PMA response with BNP (see Figure). The addition of either polyethylene glycol-adsorbed-superoxide dismutase or diphenyleneiodonium totally suppressed superoxide production. All results are shown as mean±SEM.
Conclusions: BNP suppresses PMA-stimulated, NAD(P)H oxidase-mediated, release of superoxide from normal neutrophils; this effect is lost in patients with CHF in spite of treatment.
- © 2012 by American Heart Association, Inc.