Abstract 17524: Nitrite Decreases Oxidative Stress Through Inhibition of Nuclear Factor-kappaB (NF-κB) Signaling Pathway During Chronic Ischemic-Induced Heart Failure
Background: Nitric oxide (NO) bioavailability is reduced in the setting of congestive heart failure (HF). We have previously reported that sodium nitrite (NaNO2) ameliorates acute myocardial ischemia-reperfusion (MI-R) when administered at reperfusion. NF-κB mediates cellular oxidative stress and its activation increases the severity of myocardial hypertrophy and heart failure (HF). However, no evidence exists as to whether increasing NO bioavailability via NaNO2- therapy attenuates chronic HF following acute myocardial infarction via inhibition of NF-κB activation.
Methods: Male C57/BL6J mice (n=13-15/group) underwent 60 min. of MI induced by LCA occlusion followed by 4 weeks of reperfusion. NaNO2 or saline vehicle (VEH) was administered at a dose of 165 μg/kg (intra cardiac injection) at reperfusion and then daily for 4 weeks in the drinking water (100 mg/L). Left ventricular ejection fraction (LVEF) was determined at baseline and at 4 weeks of reperfusion using high frequency ultrasound. At 4 weeks of reperfusion myocardial tissue samples were collected and analyzed by RT-qPCR, immunoblot, and electrophoretic mobility shift assay, respectively.
Results: NaNO2 administration markedly preserved LVEF (47 ± 4% vs. 32 ± 4%, p < 0.01) and improved left ventricular diastolic and systolic dimensions (LVEDD/LVESD; 4.0/3.1 mm vs. 4.5/3.9 mm, p < 0.05) at 4 weeks as compared to VEH. Malondialdehyde (MDA) and protein carbonyl content were significantly reduced (p < 0.01) in NaNO2 treated mice as compared to VEH. NaNO2 markedly reduced expression of CuZn-superoxide dismutase (SOD1) (4 fold, p < 0.05) and catalase (2 fold, p < 0.05) at 4 weeks as compared to VEH. Levels of p50 and p65 were markedly reduced (2 fold, p < 0.05) in NaNO2 treated mice as compared to VEH. Furthermore, p65 phosphorylation as well as NF-κB DNA binding activity was markedly decreased in NaNO2 treated mice.
Conclusions: Our results demonstrate that oral NaNO2 therapy improves left ventricular function secondary to suppression of myocardial oxidative stress and inhibiting NF-κB activation during heart failure following acute myocardial infarction.
Author Disclosures: K.N. Islam: None. E. Donnarumma: None. S. Bhushan: None. H. Otsuka: None. G. Cirino: None. D.J. Lefer: None.
- © 2014 by American Heart Association, Inc.