Inhaled nebulized sodium nitrite decreases pulmonary artery pressure in β-thalassemia patients with pulmonary hypertension

Yingchoncharoen, Teerapat; Rakyhao, Teewin; Chuncharunee, Suporn; Sritara, Piyamitr; Pienvichit, Pavit; Paiboonsukwong, Kittiphong; Sathavorasmith, Piyadon; Sirirat, Kanjana; Sriwantana, Thanaporn; Srihirun, Sirada; Sibmooh, Nathawut

doi:10.1016/j.niox.2017.09.010

Cited by 11 publications

(6 citation statements)

References 30 publications

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“…As confirmed in this study, NaNO 2 leads to upregulation of physiological NO signaling [increased SNOs (9,10,62)] without an apparent concurrent propensity to cause nitration (14). In humans, an injectable form of NaNO 2 is marketed as therapy for cyanide poisoning (25), and nebulized NaNO 2 was safe and well tolerated in healthy adults (44) and acutely reduced PVR in pulmonary hypertensive patients with ␤-thalassemia (56).…”

Section: Discussionsupporting

confidence: 54%

Sodium nitrite augments lungS-nitrosylation and reverses chronic hypoxic pulmonary hypertension in juvenile rats

Jankov

Daniel

Iny

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as a reversible modulator of protein function. We have previously reported that therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the juvenile rat lung, while having minimal reversing effects on vascular remodeling. We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing lung SNOs, thereby contributing to reversal of chronic hypoxic PHT. Rat pups were exposed to air or hypoxia (13% O2) from postnatal days 1 to 21. Dose-response prevention studies were conducted from days 1-21 to determine the optimal dose of NaNO2. Animals then received rescue therapy with daily s.c. NaNO2 (20 mg/kg), vehicle or were continuously exposed to iNO (20 ppm) from days 14-21. Chronic PHT secondary to hypoxia was both prevented and reversed by treatment with NaNO2. Rescue NaNO2 increased lung NO and SNO contents to a greater extent than iNO, without causing nitration. Seven lung SNO-proteins up-regulated by treatment with NaNO2 were identified by multiplex tandem mass tag spectrometry, one of which was leukotriene A4 hydrolase (LTA4H). Rescue therapy with a LTA4H inhibitor, SC57461A (10 mg/kg/d s.c.), partially reversed chronic hypoxic PHT. We conclude that NaNO2 was superior to iNO in increasing tissue NO and SNO generation and reversing chronic PHT, in part via up-regulated SNO-LTA4H.

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Section: Discussionsupporting

confidence: 54%

Sodium nitrite augments lungS-nitrosylation and reverses chronic hypoxic pulmonary hypertension in juvenile rats

Jankov

Daniel

Iny

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In patients with PAH due to HFpEF and chronic lung disease, acute inhaled nitrite lowered PAP, pulmonary capillary wedge pressures, and pulmonary vascular resistance (Simon et al, 2016). Recently, a report in five patients with echocardiographic evidence of PAH associated with b-thalassemia has suggested that acute inhaled nitrite rapidly decreases PAP, and this reverts shortly after inhalation terminates (Yingchoncharoen et al, 2018). In a pilot crossover study in 15 patients with PAH, randomized to two 7-day treatment periods (16 mmol/day nitrate vs. placebo), ingestion of a fixed dose of dietary nitrate was associated with increases in exhaled •NO and plasma and salivary NOx and was not associated with any adverse systemic hemodynamic changes.…”

Section: Nitrite and Nitrate In The Respiratory Systemmentioning

confidence: 99%

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

et al. 2020

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“…Systemic or inhaled sodium nitrite (NaNO 2 ) is an alternative NO 2 based therapy with relatively potent pulmonary vasodilator effect in the setting of experimental models of chronic hypoxic pulmonary hypertension 107,108 . Nebulized NaNO 2 acutely reduces pulmonary vascular resistance in pulmonary hypertensive patients with β-thalassemia 109 . In chronically hypoxic rat pups, subcutaneous NaNO 2 increases tissue NO, ameliorating pulmonary hypertension comparably to inhaled NO, while also increasing R-SNO content in the lung 110 .…”

Section: Nitrates and Nitrites Generating Nomentioning

confidence: 99%

Tracing the Path of Inhaled Nitric Oxide: Biological Consequences of Protein Nitrosylation

Bhatia

Elnagary

Dakshinamurti

2020

Preprint

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Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension, especially in neonates, and has been recently proposed for treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID-19. In this review, we summarize the effects of endogenous and exogenous NO on protein S-nitrosylation, which is the selective and reversible covalent attachment of a nitrogen monoxide group to the thiol side chain of cysteine. This post-translational modification targets specific cysteines based on the acid/base sequence of surrounding residues, with significant impacts on protein interactions and function. S-nitrosothiol (SNO) formation is tightly compartmentalized and enzymatically controlled, but also propagated by non-enzymatic transnitrosylation of downstream protein targets. Redox-based nitrosylation and denitrosylation pathways dynamically regulate the equilibrium of SNO-proteins. We review the physiological roles of SNO proteins, including nitrosohemoglobin and autoregulation of blood flow through hypoxic vasodilation, and pathological effects of nitrosylation including inhibition of critical vasodilator enzymes; and discuss the intersection of NO source and dose with redox environment, in determining the effects of protein nitrosylation.

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Inhaled nebulized sodium nitrite decreases pulmonary artery pressure in β-thalassemia patients with pulmonary hypertension

Cited by 11 publications

References 30 publications

Sodium nitrite augments lungS-nitrosylation and reverses chronic hypoxic pulmonary hypertension in juvenile rats

Sodium nitrite augments lungS-nitrosylation and reverses chronic hypoxic pulmonary hypertension in juvenile rats

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

Tracing the Path of Inhaled Nitric Oxide: Biological Consequences of Protein Nitrosylation

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