Dietary inorganic nitrate mobilizes circulating angiogenic cells

Heiß, Christian; Meyer, Christian; Totzeck, Matthias; Hendgen‐Cotta, Ulrike B.; Heinen, Yvonne; Luedike, Peter; Keymel, Stefanie; Ayoub, Nassim; Lundberg, Jon O.; Weitzberg, Eddie; Kelm, Malte; Rassaf, Tienush

doi:10.1016/j.freeradbiomed.2012.02.051

Cited by 69 publications

(54 citation statements)

References 43 publications

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“…Nitrite is regarded as a reservoir for NO • , which is selectively activated under physiological 30,36 and pathophysiological conditions. 27,43,49 We here demonstrate that the rIPC stimulus leads to a transfer of nitrite to the myocardium where it is then reduced by Mb to bioactive NO…”

Section: Signal Transfer and Transduction Into Cardioprotectionmentioning

confidence: 56%

“…To confirm further the relevance of generated nitrite for cardioprotection, we increased the endogenous nitrite levels by dietary nitrate supplementation 27 and performed the rIPC procedure. Administration of the conditioned plasma to mouse hearts reduced infarct sizes to 25±3%, and nitrite scavenging with sulfanilamide again abolished these protective effects (data not shown).…”

Section: Human Plasma Nitrite From Remote Conditioning Protects From mentioning

confidence: 99%

“…21 We and others have recently demonstrated that exogenous supplementation with near physiological nitrite doses has implications for tissue protection under pathological conditions. This pertains to single nitrite injections, chronically administered nitrite, 17,[22][23][24][25][26][27][28][29] and remarkably also to nitrite administered before the onset of ischemia. 26 Finally, we recently demonstrated that nitrite contributes at physiological levels to the mechanisms causing vessels to dilate when challenged with hypoxia.…”

mentioning

confidence: 99%

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Circulating Nitrite Contributes to Cardioprotection by Remote Ischemic Preconditioning

Rassaf

Totzeck

Hendgen‐Cotta

et al. 2014

Circulation Research

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Rationale: Remote ischemic preconditioning (rIPC) with short episodes of ischemia/reperfusion (I/R) of an organ remote from the heart is a powerful approach to protect against myocardial I/R injury. The signal transduction pathways for the cross talk between the remote site and the heart remain unclear in detail.Objective: To elucidate the role of circulating nitrite in cardioprotection by rIPC. Methods and Results: Mice were subjected to 4 cycles of no-flow ischemia with subsequent reactive hyperemia within the femoral region and underwent in vivo myocardial I/R (30 minutes/5 minutes or 24 hours). The mouse experiments were conducted using genetic and pharmacological approaches. Shear stress-dependent stimulation of endothelial nitric oxide synthase within the femoral artery during reactive hyperemia yielded substantial release of nitric oxide, subsequently oxidized to nitrite and transferred humorally to the myocardium. Within the heart, reduction of nitrite to nitric oxide by cardiac myoglobin and subsequent S-nitrosation of mitochondrial membrane proteins reduced mitochondrial respiration, reactive oxygen species formation, and myocardial infarct size. Pharmacological and genetic inhibition of nitric oxide/nitrite generation by endothelial nitric oxide synthase at the remote site or nitrite bioactivation by myoglobin within the target organ abrogated the cardioprotection by rIPC. Transfer experiments of plasma from healthy volunteers subjected to rIPC of the arm identified plasma nitrite as a cardioprotective agent in isolated Langendorff mouse heart preparations exposed to I/R. Conclusions:

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Section: Signal Transfer and Transduction Into Cardioprotectionmentioning

confidence: 56%

Section: Human Plasma Nitrite From Remote Conditioning Protects From mentioning

confidence: 99%

mentioning

confidence: 99%

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Circulating Nitrite Contributes to Cardioprotection by Remote Ischemic Preconditioning

Rassaf

Totzeck

Hendgen‐Cotta

et al. 2014

Circulation Research

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304

267

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“…Nitrite reduces the increase in pulmonary arterial pressure induced by hypoxia in healthy volunteers, an effect that persisted even 1 h after cessation of nitrite infusion when plasma levels returned back to the baseline [9]. A single dose of oral sodium nitrate elevated angiogenic markers and recruited circulating angiogenic cells in healthy human volunteers [10]. Improved angiogenesis was confirmed in an experimental animal model of chronic hind limb ischemia following chronic oral supplementation [11].…”

Section: Aimmentioning

confidence: 86%

A Randomized double-blind placebo-controlled Crossover Trial of Sodium Nitrate in Patients With Stable Angina INAS

Schwarz¹,

Singh²,

Parasuraman³

et al. 2016

Future Cardiol.

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In an aging western population, a significant number of patients continue to suffer from angina once all revascularization and optimal medical treatment options are exhausted. Under experimental conditions, oral supplementation with inorganic nitrate was shown to exhibit a blood pressure-lowering effect, and has also been shown to promote angiogenesis, improve endothelial dysfunction and mitochondrial efficiency in skeletal muscle. It is unknown whether similar changes occur in cardiac muscle. In the current study, we investigate whether oral sodium nitrate treatment will improve myocardial ischemia in patients with stable angina.

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“…These observations contrast with two other published studies. In 2012 Heiss et al demonstrated an increase in FMD in response to dietary NO 3 − in healthy volunteers and suggested that this effect was due to an increased mobilization of circulating angiogenic cells [119]. More recently the same group has shown, in studies delivering NO 3 − through spinach consumption, a dose-dependent improvement in FMD responses with doses above ß4 mmol [120].…”

Section: No 2 − /No 3 − and Vascular Functionmentioning

confidence: 99%

A ‘green’ diet‐based approach to cardiovascular health? Is inorganic nitrate the answer?

Rathod

Velmurugan

Ahluwalia

2015

Molecular Nutrition Food Res

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Ingestion of fruit and vegetables rich in inorganic nitrate (NO(3)(-)) has emerged as an effective method for acutely elevating vascular nitric oxide (NO) levels through formation of an NO(2)(-) intermediate. As such a number of beneficial effects of NO(3)(-) and NO(2)(-) ingestion have been demonstrated including reductions in blood pressure, measures of arterial stiffness and platelet activity. The pathway for NO generation from such dietary interventions involves the activity of facultative oral microflora that facilitate the reduction of inorganic NO(3)(-), ingested in the diet, to inorganic NO(2)(-). This NO(2)(-) then eventually enters the circulation where, through the activity of one or more of a range of distinct NO(2)(-) reductases, it is chemically reduced to NO. This pathway provides an alternative route for in vivo NO generation that could be utilized for therapeutic benefit in those cardiovascular disease states where reduced bioavailable NO is thought to contribute to pathogenesis. Indeed, the cardiovascular benefits of NO(2)(-) and NO(3)(-) are now starting to be translated in patients in several clinical trials. In this review, we discuss recent evidence supporting the potential utility of delivery of NO(3)(-) or NO(2)(-) for the treatment of cardiovascular diseases.

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Dietary inorganic nitrate mobilizes circulating angiogenic cells

Cited by 69 publications

References 43 publications

Circulating Nitrite Contributes to Cardioprotection by Remote Ischemic Preconditioning

Circulating Nitrite Contributes to Cardioprotection by Remote Ischemic Preconditioning

A Randomized double-blind placebo-controlled Crossover Trial of Sodium Nitrate in Patients With Stable Angina INAS

A ‘green’ diet‐based approach to cardiovascular health? Is inorganic nitrate the answer?

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