Nitrite Therapy Ameliorates Myocardial Dysfunction via H2S and Nuclear Factor‐Erythroid 2‐Related Factor 2 (Nrf2)‐Dependent Signaling in Chronic Heart Failure. Issue 8 (29th July 2016)

• Record Type: Journal Article
• Authors: Donnarumma, Erminia; Bhushan, Shashi; Bradley, Jessica M.; Otsuka, Hiroyuki; Donnelly, Erinn L.; Lefer, David J.; Islam, Kazi N.
• Is Part Of: Journal of the American Heart Association. Volume 5:Issue 8(2016)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-07-29
• Subjects: antioxidant -- H2S -- heart failure -- nitric oxide -- Nrf2 -- reactive oxygen species; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.116.003551
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : Background: Bioavailability of nitric oxide (NO) and hydrogen sulfide (H2 S) is reduced in heart failure (HF). Recent studies suggest cross‐talk between NO and H2 S signaling. We previously reported that sodium nitrite (NaNO2 ) ameliorates myocardial ischemia‐reperfusion injury and HF. Nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) regulates the antioxidant proteins expression and is upregulated by H2 S. We examined the NaNO2 effects on endogenous H2 S bioavailability and Nrf2 activation in mice subjected to ischemia‐induced chronic heart failure (CHF). Methods and Results: Mice underwent 60 minutes of left coronary artery occlusion and 4 weeks of reperfusion. NaNO2 (165 μg/kgic) or vehicle was administered at reperfusion and then in drinking water (100 mg/L) for 4 weeks. Left ventricular (LV), ejection fraction (EF), LV end diastolic (LVEDD) and systolic dimensions (LVESD) were determined at baseline and at 4 weeks of reperfusion. Myocardial tissue was analyzed for oxidative stress and respective gene/protein‐related assays. We found that NaNO2 therapy preserved LVEF, LVEDD and LVSD at 4 weeks during ischemia‐induced HF. Myocardial malondialdehyde and protein carbonyl content were significantly reduced in NaNO2 ‐treated mice as compared to vehicle, suggesting a reduction in oxidative stress. NaNO2 therapy markedly increased expression of Cu, Zn‐superoxide dismutase, catalase, and glutathione peroxidase during 4 weeks of reperfusion. Furthermore, NaNO2 upregulated the activity of Nrf2, as well as H2 S‐producing enzymes, and ultimately increased H2 S bioavailability in ischemia‐induced CHF in mice as compared with vehicle. Conclusions: Our results demonstrate that NaNO2 therapy significantly improves LV function via increasing H2 S bioavailability, Nrf2 activation, and antioxidant defenses.