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Nitrite Therapy Ameliorates Myocardial Dysfunction via H 2 S and Nuclear Factor ‚Äź Erythroid 2 ‚Äź Related Factor 2 (Nrf2) ‚Äź Dependent Signaling in Chronic Heart Failure

View Article: PubMed Central - PubMed

ABSTRACT

Background: Bioavailability of nitric oxide (NO) and hydrogen sulfide (H2S) is reduced in heart failure (HF). Recent studies suggest cross‐talk between NO and H2S 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 H2S. We examined the NaNO2 effects on endogenous H2S 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 H2S‐producing enzymes, and ultimately increased H2S bioavailability in ischemia‐induced CHF in mice as compared with vehicle.

Conclusions: Our results demonstrate that NaNO2 therapy significantly improves LV function via increasing H2S bioavailability, Nrf2 activation, and antioxidant defenses.

No MeSH data available.


Related in: MedlinePlus

Effects of nitrite on oxidative stress during ischemia‚Äźinduced CHF. Total antioxidant capacity in both heart tissues (A) and plasma (B) were measured by the Trolox equivalent capacity assay. Malondialdehyde (C) and carbonyl contents (D) were measured in total protein extracts obtained from mouse heart tissues. The number inside the bar denotes the number of animals per group. Differences in data between the groups were compared using Prism 6 (GraphPad Software, La Jolla, CA) with nonparametric test (Wilcoxon rank sum test). CHF indicates chronic heart failure.
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jah31681-fig-0004: Effects of nitrite on oxidative stress during ischemia‚Äźinduced CHF. Total antioxidant capacity in both heart tissues (A) and plasma (B) were measured by the Trolox equivalent capacity assay. Malondialdehyde (C) and carbonyl contents (D) were measured in total protein extracts obtained from mouse heart tissues. The number inside the bar denotes the number of animals per group. Differences in data between the groups were compared using Prism 6 (GraphPad Software, La Jolla, CA) with nonparametric test (Wilcoxon rank sum test). CHF indicates chronic heart failure.

Mentions: We studied the effect of oral nitrite therapy on total antioxidant capacity and oxidative damage during ischemia‚Äźinduced CHF in mice. Total antioxidant capacity was estimated by Trolox equivalent capacity assay in both heart tissues and plasma (Figure¬†4A and 4B) while oxidative modifications were determined by measuring MDA and protein carbonyl contents in myocardial tissue samples (Figure¬†4C and 4D). Figure¬†4A and 4B show that nitrite treatment increased the total antioxidant capacity in both myocardium and plasma obtained from ischemia‚Äźinduced CHF mice. Additionally, Figure¬†4C and 4D show that levels of both MDA and protein carbonyl contents were significantly decreased in nitrite‚Äźtreated CHF mice as compared with VEH. For further confirmation of the antioxidant effects of oral nitrite therapy, we also measured the antioxidant proteins levels. Figure¬†5A through 5G shows that nitrite treatment increased both myocardial mRNA and protein levels of SOD1, catalase, and GPX in ischemia‚Äźinduced CHF mice as compared with VEH.


Nitrite Therapy Ameliorates Myocardial Dysfunction via H 2 S and Nuclear Factor ‚Äź Erythroid 2 ‚Äź Related Factor 2 (Nrf2) ‚Äź Dependent Signaling in Chronic Heart Failure
Effects of nitrite on oxidative stress during ischemia‚Äźinduced CHF. Total antioxidant capacity in both heart tissues (A) and plasma (B) were measured by the Trolox equivalent capacity assay. Malondialdehyde (C) and carbonyl contents (D) were measured in total protein extracts obtained from mouse heart tissues. The number inside the bar denotes the number of animals per group. Differences in data between the groups were compared using Prism 6 (GraphPad Software, La Jolla, CA) with nonparametric test (Wilcoxon rank sum test). CHF indicates chronic heart failure.
© Copyright Policy - creativeCommonsBy-nc-nd
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5015282&req=5

jah31681-fig-0004: Effects of nitrite on oxidative stress during ischemia‚Äźinduced CHF. Total antioxidant capacity in both heart tissues (A) and plasma (B) were measured by the Trolox equivalent capacity assay. Malondialdehyde (C) and carbonyl contents (D) were measured in total protein extracts obtained from mouse heart tissues. The number inside the bar denotes the number of animals per group. Differences in data between the groups were compared using Prism 6 (GraphPad Software, La Jolla, CA) with nonparametric test (Wilcoxon rank sum test). CHF indicates chronic heart failure.
Mentions: We studied the effect of oral nitrite therapy on total antioxidant capacity and oxidative damage during ischemia‚Äźinduced CHF in mice. Total antioxidant capacity was estimated by Trolox equivalent capacity assay in both heart tissues and plasma (Figure¬†4A and 4B) while oxidative modifications were determined by measuring MDA and protein carbonyl contents in myocardial tissue samples (Figure¬†4C and 4D). Figure¬†4A and 4B show that nitrite treatment increased the total antioxidant capacity in both myocardium and plasma obtained from ischemia‚Äźinduced CHF mice. Additionally, Figure¬†4C and 4D show that levels of both MDA and protein carbonyl contents were significantly decreased in nitrite‚Äźtreated CHF mice as compared with VEH. For further confirmation of the antioxidant effects of oral nitrite therapy, we also measured the antioxidant proteins levels. Figure¬†5A through 5G shows that nitrite treatment increased both myocardial mRNA and protein levels of SOD1, catalase, and GPX in ischemia‚Äźinduced CHF mice as compared with VEH.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Bioavailability of nitric oxide (NO) and hydrogen sulfide (H2S) is reduced in heart failure (HF). Recent studies suggest cross‐talk between NO and H2S 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 H2S. We examined the NaNO2 effects on endogenous H2S 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 H2S‐producing enzymes, and ultimately increased H2S bioavailability in ischemia‐induced CHF in mice as compared with vehicle.

Conclusions: Our results demonstrate that NaNO2 therapy significantly improves LV function via increasing H2S bioavailability, Nrf2 activation, and antioxidant defenses.

No MeSH data available.


Related in: MedlinePlus