Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation

Bailey, Jenna; Feelisch, Martin; Horowitz, John D.; Frenneaux, Michael; Madhani, Melanie

doi:10.1016/j.pharmthera.2014.06.009

Cited by 49 publications

(37 citation statements)

References 214 publications

(236 reference statements)

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“…The nitrate–nitrite–NO pathway has been shown to regulate blood pressure and hypoxic vasodilatation and improve exercise performance and mitochondrial efficiency (Bailey et al ., 2014). Our work and those of others have demonstrated that infusions of sodium nitrite in healthy subjects dilate forearm vasculature, with significant potentiation during hypoxia, thereby preferentially dilating capacitance vessels (Maher et al ., 2008; van Faassen et al ., 2009; Totzeck et al ., 2012; Kapil et al ., 2014).…”

Section: A Novel Therapeutic Pathway: Nitrate–nitrite–nomentioning

confidence: 99%

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Loudon

Noordali

Gollop

et al. 2016

British J Pharmacology

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Many conditions culminate in heart failure (HF), a multi‐organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence‐base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite.

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Section: A Novel Therapeutic Pathway: Nitrate–nitrite–nomentioning

confidence: 99%

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Loudon

Noordali

Gollop

et al. 2016

British J Pharmacology

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“…Работами групп F.J. Larsen [58][59][60] и S.J. Bailey [9,10] было найдено, что про-исходит уменьшение расхода кислорода в работа-ющих мышцах при физическом упражнении после краткосрочного добавления нитрата в диету у здо-ровых лиц. Приведем рассуждения F.J. Larsen et al [59] вместе со ссылками, которые дают авторы: «Этот эффект был большой неожиданностью, пото-му что классическая физиология упражнений пред-писывает минимальные колебания расхода кисло-рода на определенной рабочей нагрузке для любого лица, уровня тренированности [70], возраста или диеты [7].…”

Section: No изменяет эффективность окислительного фосфорилированияunclassified

Nitric oxide and hypoxia at adaptation to muscular work (brief review)

Radchenko

2016

Rev Clin Pharm Drug Ther

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The The last two decades there has been a growing interest in the nitric oxide (NO) function in the body of a healthy person. In the study, two very specific problems are discussed: a) the NO involvement in mechanisms of adaptation at muscular work under hypoxia conditions, and b) the inorganic nitrate supplementation in athlete’s diet with the aim of sports performance improvement. The reorganizations that occur in the heart vasculature and in skeletal muscle for providing muscle work under hypoxia conditions examined. The named problems are particularly relevant in contemporary sports in which the adding of hypoxic exposure on a body of training persons as well as the inorganic nitrate in sports nutrition application as added means to special performance improvement. Raise the problem of the hypoxia and inorganic nitrate mutual exploitation in the training process.

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“…An abundance of research has focused on defining the vasoactive/cardioprotective roles of NO 2 À with many studies suggesting that the reduction of NO 2 À to NO compliments the well-understood NOS pathway of NO production, particularly when NOS function becomes uncoupled or otherwise impaired (reviewed by 34,35 ). The vascular responses to NO 2 À infusion presented herein support this notion.…”

Section: Effects Of Inorganic No 2 à Infusion On Skeletal Muscle Bf Amentioning

confidence: 99%

Skeletal Muscle Vascular Control During Exercise

Ferguson

Glean

Holdsworth

et al. 2015

J Cardiovasc Pharmacol Ther

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The nitric oxide synthase (NOS)-independent pathway of nitric oxide (NO) production in which nitrite (NO2 (-)) is reduced to NO may have therapeutic applications for those with cardiovascular diseases in which the NOS pathway is downregulated. We tested the hypothesis that NO2 (-) infusion would reduce mean arterial pressure (MAP) and increase skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise in the face of NOS blockade via L-NAME. Following infusion of L-NAME (10 mg kg(-1), L-NAME), male Sprague-Dawley rats (3-6 months, n = 8) exercised without N(G)-nitro-L arginine methyl ester (L-NAME) and after infusion of sodium NO2 (-) (7 mg kg(-1); L-NAME + NO2 (-)). MAP and hindlimb skeletal muscle BF (radiolabeled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). Across group comparisons were made with a published control data set (n = 11). Relative to L-NAME, NO2 (-) infusion significantly reduced MAP (P < 0.03). The lower MAP in L-NAME+NO2 (-) was not different from healthy control animals (control: 137 ± 3 L-NAME: 157 ± 7, L-NAME + NO2 (-): 136 ± 5 mm Hg). Also, NO2 (-) infusion significantly increased VC when compared to L-NAME (P < 0.03), ultimately negating any significant differences from control animals (control: 0.78 ± 0.05, L-NAME: 0.57 ± 0.03, L-NAME + NO2 (-); 0.69 ± 0.04 mL min(-1) 100 g(-1) mm Hg(-1)) with no apparent fiber-type preferential effect. Overall, hindlimb BF was decreased significantly by L-NAME; however, in L-NAME + NO2 (-), BF improved to a level not significantly different from healthy controls (control: 108 ± 8, L-NAME: 88 ± 3, L-NAME + NO2 (-): 94 ± 6 mL min(-1) 100 g(-1), P = 0.38 L-NAME vs L-NAME + NO2 (-)). Individuals with diseases that impair NOS activity, and thus vascular function, may benefit from a NO2 (-)-based therapy in which NO bioavailability is elevated in an NOS-independent manner.

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Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation

Cited by 49 publications

References 214 publications

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Nitric oxide and hypoxia at adaptation to muscular work (brief review)

Skeletal Muscle Vascular Control During Exercise

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