Sodium nitrite improves hypertension-induced myocardial dysfunction by mechanisms involving cardiac S-nitrosylation

Neto-Neves, Evandro M.; Pinheiro, Lucas C.; Nogueira, Renato C.; Portella, Rafael de Lima; Batista, Rose I.M.; Tanus‐Santos, José Eduardo

doi:10.1016/j.yjmcc.2019.06.012

Cited by 18 publications

(9 citation statements)

References 55 publications

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“…Nitrite also reduced the vascular 50 and cardiac remodelling 51 in a renovascular model of hypertension. In accordance, nitrite improved cardiac function in normotensive and hypertensive rats, while it attenuated the cardiac hypertrophy and the rise in blood pressure in 2K1C rats by mechanisms involving increased S‐nitrosothiol concentrations and protein nitrosylation in the myocardium 52 . In L‐NAME‐induced hypertensive rats, nitrite attenuated cardiac remodelling by inhibiting AngII‐induced TGF‐β activation signalling pathway 53 .…”

Section: Nitrate‐nitrite‐no Biology In the Cardiovascular Systemmentioning

confidence: 72%

“…In accordance, nitrite improved cardiac function in normotensive and hypertensive rats, while it attenuated the cardiac hypertrophy and the rise in blood pressure in 2K1C rats by mechanisms involving increased S-nitrosothiol concentrations and protein nitrosylation in the myocardium. 52 In L-NAMEinduced hypertensive rats, nitrite attenuated cardiac remodelling by inhibiting AngII-induced TGF-β activation signalling pathway. 53 Sodium nitrite treatment also decreased VSMC proliferation via the NO-dependent induction of the cyclindependent kinase inhibitor p21(Waf1/Cip1) in an in vivo rat model of vascular injury associated with increased XOR activity, which is an enzyme with well-known nitrite reductase activity.…”

Section: Nitrate and Nitrite Reduce Cardiovascular Remodelling In Hmentioning

confidence: 99%

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Nitrate and nitrite‐based therapy to attenuate cardiovascular remodelling in arterial hypertension

Guimaraes

Batista

Tanus‐Santos

2020

Basic Clin Pharma Tox

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Elevated blood pressure is a leading global contributor to death and disability worldwide, and in 2010, about 1.4 billion people were hypertensive. 1 Hypertension involves a complex interplay of environmental and pathophysiological factors that affect multiple systems and is the most common risk factor that predisposes to cardiovascular diseases. 2 Through its effects on target organs, hypertension has been associated with a variety of cardiovascular comorbidities such as coronary artery disease, stroke, chronic kidney disease, metabolic syndrome and dyslipidaemia. 3 Maintenance of normal blood pressure is dependent on the balance between the cardiac output and vascular resistance.

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Section: Nitrate‐nitrite‐no Biology In the Cardiovascular Systemmentioning

confidence: 72%

Section: Nitrate and Nitrite Reduce Cardiovascular Remodelling In Hmentioning

confidence: 99%

Nitrate and nitrite‐based therapy to attenuate cardiovascular remodelling in arterial hypertension

Guimaraes

Batista

Tanus‐Santos

2020

Basic Clin Pharma Tox

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“…This pattern of effect on LV contractile function is entirely consistent with prior studies reporting similar direct myocardial effects of NO donors and NO-cGMP signaling on the onset of relaxation and diastolic stiffness, both in isolated preparations and in humans in vivo ( 18 , 20 , 28 , 29 ). At a mechanistic level, such actions are considered to involve cGMP/protein kinase G (PKG)-mediated phosphorylation of troponin I and titin in cardiomyocytes ( 19 , 30 – 32 ), although other NO-mediated mechanisms such as altered S-nitrosylation of proteins ( 33 , 34 ) or an effect on sympathetic nerve activity ( 35 , 36 ) may have a role. Taken together, the data from the intracoronary infusion study suggest that inorganic nitrite has a direct and selective action on the myocardium to reduce ventricular stiffness and hasten the onset of relaxation.…”

Section: Discussionmentioning

confidence: 99%

Direct cardiac versus systemic effects of inorganic nitrite on human left ventricular function

O’Gallagher

Cabaco

Ryan

et al. 2021

American Journal of Physiology-Heart and Circulatory Physiology

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Background Inorganic nitrite generates nitric oxide (NO) in vivo and is considered a potential therapy in settings where endogenous NO bioactivity is reduced and left ventricular (LV) function impaired. However, the effects of nitrite on human cardiac contractile function, and the extent to which these are direct or indirect, are unclear. Methods and Results We studied 40 patients undergoing diagnostic cardiac catheterisation who had normal LV systolic function and were not found to have obstructive coronary disease. They received either an intracoronary sodium nitrite infusion (8.7-26 mmol/min, n=20) or an intravenous sodium nitrite infusion (50 mg/kg/min, n=20). LV pressure-volume relations were recorded. The primary end point was LV end-diastolic pressure (LVEDP) while secondary end points included indices of LV systolic and diastolic function. Intracoronary nitrite infusion induced a significant reduction in LVEDP, LV end-diastolic pressure-volume relationship (EDPVR) and the time to LV end-systole (LVEST) but had no significant effect on measures of LV systolic function or systemic haemodynamics. Intravenous nitrite infusion induced greater effects, with significant decreases in LVEDP, EDPVR, LVEST, LV dP/dtmin, tau, and mean arterial pressure. Conclusions These results indicate that inorganic nitrite has modest direct effects on human LV diastolic function, independent of LV loading conditions and without affecting LV systolic properties. The systemic administration of nitrite has larger effects on LV diastolic function which are related to reduction in both preload and afterload. These effects of inorganic nitrite indicate a favourable profile for conditions characterized by LV diastolic dysfunction, e.g. heart failure with preserved ejection fraction.

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“…Animal experiments have confirmed the effectiveness of NO donor, such as organic nitrates and nitrites, in alleviating myocardial ischemiareperfusion injury (14,15). These drugs may reduce infarct area and improve cardiomyocyte survival rate by reducing platelet aggregation, alleviating inflammation, and reducing oxidative stress (16)(17)(18)(19)(20). Although many animal experiments have confirmed that nitrite drugs can protect against myocardial ischemia-reperfusion injury, the clinical trial results of these drugs are not ideal, and their efficacy in patients with acute coronary syndrome (ACS) is still uncertain.…”

Section: Introductionmentioning

confidence: 88%

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

Cai¹,

Zhang²,

Shalamu³

et al. 2022

Ann Transl Med

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Background: This study aimed to verify the effect of soluble guanylate cyclase (sGC) stimulator vericiguat on myocardial ischemia-reperfusion injury and explore its mechanism.Methods: A myocardial ischemia-reperfusion injury model of mice was established and intravenous administration was performed 2 minutes before reperfusion. Triphenyltetrazolium chloride (TTC) staining and echocardiography were used to verify the effect of vericiguat on myocardial ischemia-reperfusion injury in the infarct area, and immunofluorescence was used to observe myocardial pathological changes at different time points after reperfusion. Quantitative proteomics was conducted to analysis the main differentially expressed proteins after drug intervention. The distribution of endothelial cells and sGC after myocardial ischemia-reperfusion injury in mice was observed by immunofluorescence. RNA sequencing of endothelial cells was used to search for differentially expressed molecules. Thioflavin-S staining was used to observe the effect of vericiguat on improving the nonrecurrence phenomenon and reducing the infarct size after reperfusion.Results: The effect of the sGC stimulator vericiguat on myocardial ischemia-reperfusion injury was verified, and myocardial microcirculation significantly increased after drug intervention. Quantitative proteomics found that the protein expression of myocardial tissue in the ischemia-reperfusion area was not significantly different in the drug intervention group, except for increased adenosine triphosphate (ATP) activity. Vericiguat, nitroglycerin, and nitrite did not directly affect apoptosis or cell viability. RNA sequencing of human umbilical vein endothelial cells screened the upregulated antioxidant response.Conclusions: SGC stimulator vericiguat ameliorated myocardial ischemia-reperfusion injury through indirect pathways of improving microcirculation.

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Sodium nitrite improves hypertension-induced myocardial dysfunction by mechanisms involving cardiac S-nitrosylation

Cited by 18 publications

References 55 publications

Nitrate and nitrite‐based therapy to attenuate cardiovascular remodelling in arterial hypertension

Nitrate and nitrite‐based therapy to attenuate cardiovascular remodelling in arterial hypertension

Direct cardiac versus systemic effects of inorganic nitrite on human left ventricular function

Soluble guanylate cyclase (sGC) stimulator vericiguat alleviates myocardial ischemia-reperfusion injury by improving microcirculation

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