Abstract 264: Nitrite Therapy Ameliorates Myocardial Injury via H2S and Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2)-Dependent Signaling in Chronic Heart Failure
Background: Nitric oxide (NO) and hydrogen sulfide (H2S) are reduced in congestive heart failure. Recent studies suggest cross-talk between NO and H2S signaling. We previously reported that sodium nitrite (NaNO2) significantly ameliorates myocardial ischemia-reperfusion injury and heart failure. Nrf2 regulates the expression of antioxidant protein genes and is upregulated by H2S. We examined the effects of NaNO2 therapy on endogenous H2S bioavailability and Nrf2 activation in mice subjected to ischemia-induced heart failure.
Materials and Methods: Mice underwent 60 min. of left coronary artery occlusion and 4 weeks (WKS) of reperfusion. NaNO2 (165 μg/kg) or saline vehicle (VEH) was administered at reperfusion and then in drinking water (100 mg/L) for 4 wks. Left ventricular ejection fraction (LVEF) was determined at baseline and 4 wks of reperfusion. Myocardial tissue was collected and analyzed for oxidative stress status and respective gene/protein levels.
Results: NaNO2 therapy preserved LVEF (47 ± 4% vs. 32 ± 4%, p < 0.01) and LV diastolic and systolic dimensions (LVEDD/LVESD; 4.0/3.1 mm vs. 4.5/3.9 mm, p < 0.05) at 4 wks. MDA and protein carbonyl contents were significantly reduced in NaNO2 treated mice as compared to VEH. NaNO2 markedly increased expression of CuZn-superoxide dismutase and catalase at 4 wks. Furthermore, NaNO2 increased mRNA levels of H2S producing enzymes and H2S bioavailabilty. Cardiac Nrf2 activation was also observed with NaNO2 therapy.
Conclusions: Our results demonstrate that NaNO2therapy significantly improves left ventricular function via by increasing H2S bioavailability, activation of Nrf2, and increased antioxidant defenses.1
Author Disclosures: K.N. Islam: None. E. Donnarumma: None. S. Bhushan: None. D.J. Lefer: 7. Ownership Interest; Significant; is a participant of a pending U. S. patent filed on 15 nov. 2007 (# 61/003150) regarding the use of nitrite salts in chronic ischemia.. 8. Consultant/Advisory Board; Significant; Is on the Scientifc advisory board of Theravasc, Inc. Theravasc is currently developing sodium nitrite for the treatment of cardiovascular diseases..
- © 2015 by American Heart Association, Inc.