Formation of new bioactive organic nitrites and their identification with gas chromatography–mass spectrometry and liquid chromatography coupled to nitrite reduction

Nilsson, Kristofer F.; Lundgren, Michael; Agvald, Per; Adding, Christofer; Linnarsson, Dag; Gustafsson, Lars E.

doi:10.1016/j.bcp.2011.04.005

Cited by 10 publications

(26 citation statements)

References 37 publications

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“…We used pre-treatment, which is not always clinically possible, and we did not compare PDNO with another classic NO donor but with inorganic nitrite (the vehicle). Inorganic nitrite was included in the placebo vehicle since the synthesis of PDNO also forms a certain amount of inorganic nitrite in the solution [16]. The vehicle-treated group received a solution with 28 mM of inorganic nitrite to achieve a similar load of nitric oxide species as the PDNO group (17 mM of PDNO and 11 mM of inorganic nitrite).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the vehicle-treated animals received an identical load of nitric oxide species in the form of inorganic nitrite that the PDNO group received in PDNO and inorganic nitrite as well as an identical load of 1,2-propanediol. The organic mononitrites of 1,2-propanediol was synthesized as previously described, and the inorganic nitrite content in the PDNO solution was a consequence of the method of synthesis [16]. Blood samples were taken from the left renal vein, carotid artery, and jugular vein at baseline, prior to treatment, prior and directly following the release of the clamp, and every hour after treatment was started.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, a mixture of novel organic mononitrites of 1,2-propanediol was synthesized, chemically characterized, and shown to be an efficacious vasodilator treatment in experimental pulmonary hypertension [16]. The advantages of this composition of organic nitrites include very rapid deployment of NO in the tissue, easily controllable intravenous use, and minor development of methemoglobin.…”

Section: Introductionmentioning

confidence: 99%

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The novel nitric oxide donor PDNO attenuates ovine ischemia-reperfusion induced renal failure

Nilsson

Sandin

Gustafsson

et al. 2017

ICMx

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BackgroundRenal ischemia-reperfusion injury is a common cause of acute kidney injury in intensive care and surgery. Recently, novel organic mononitrites of 1,2-propanediol (PDNO) were synthesized and shown to rapidly and controllably deploy nitric oxide in the circulation when administered intravenously. We hypothesized that intravenous infusion of PDNO during renal ischemia reperfusion would improve post-ischemic renal function and microcirculation.MethodsSixteen sheep were anesthetized, mechanically ventilated, and surgically instrumented. The left renal artery was clamped for 90 min, and the effects of ischemia were studied for a total of 8 h. Fifteen minutes prior to the release of the clamp, intravenous infusions of PDNO (n = 8) or vehicle (1,2 propanediol + inorganic nitrite, n = 8) were initiated (180 nmol/kg/min for 30 min, thereafter 60 nmol/kg/min for the remainder of the experiment).ResultsRenal artery blood flow, cortical and medullary perfusion, and diuresis and creatinine clearance decreased in the left kidney post ischemia. However, in the sheep treated with PDNO, diuresis and creatinine clearance in the left kidney were significantly higher post ischemia compared to vehicle-treated animals (1.7 ± 0.5 vs 0.7 ± 0.3 ml/kg/h, p = 0.04 and 7.5 ± 2.1 vs 1.7 ± 0.6 ml/min, p = 0.02, respectively). Left renal medullary perfusion and oxygen uptake were higher in the PDNO group (73 ± 9 vs 37 ± 5% of baseline, p = 0.004 and 2.6 ± 0.4 vs 1.6 ± 0.3 ml/min, p = 0.02, respectively). PDNO significantly increased renal oxygen consumption and reduced the oxygen utilization for sodium reabsorption (p = 0.03 for both). Mean arterial blood pressure was significantly reduced by PDNO (83 ± 3 vs 94 ± 3 mmHg, p = 0.02) but was still within normal limits. Total renal blood flow was not affected, and there were no signs of increased blood methemoglobin concentrations or tachyphylaxis.ConclusionsThe novel nitric oxide donor PDNO improved renal function after ischemia. PDNO also prevented the persistent reduction in medullary perfusion during reperfusion and improved renal oxygen utilization without severe side effects.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The novel nitric oxide donor PDNO attenuates ovine ischemia-reperfusion induced renal failure

Nilsson

Sandin

Gustafsson

et al. 2017

ICMx

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“…NO donors of organic nitrite type are converted to NO in vivo and in contrast to organic nitrates they exhibited little or no tolerance . Ethyl nitrite has been suggested as an inhaled therapeutic but might evoke significant methemoglobin formation .…”

Section: Introductionmentioning

confidence: 99%

“…Ethyl nitrite has been suggested as an inhaled therapeutic but might evoke significant methemoglobin formation . Recently, we synthesized novel organic nitrites and found that the polarity of the individual organic nitrite molecule determined its relative selectivity for vasodilation in the pulmonary and systemic circulations …”

Section: Introductionmentioning

confidence: 99%

Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism

Nilsson

Gustafsson

2019

Pharmacology Res & Perspec

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Acute pulmonary embolism may cause right heart failure due to increased pulmonary vascular resistance and arterial hypoxemia. Effective vasodilator therapy of the pulmonary hypertension is highly needed. Therefore, we investigated the effects of a newly developed effective pulmonary vasodilator, the organic mononitrites of 1,2‐propanediol (PDNO), in a rabbit model of acute pulmonary embolism. In anesthetized and ventilated rabbits, systemic and pulmonary hemodynamics, exhaled nitric oxide (NO), plasma nitrite concentration, and blood gases were monitored. First, dose–response experiments with intravenous and left heart ventricle infusions of PDNO and inorganic nitrite were done in naive animals and in pulmonary hypertension induced by a thromboxane A2 analogue. Second, acute pulmonary embolism was induced and either PDNO or placebo were administered intravenously within 20 minutes and evaluated within 1 hour after pulmonary embolization. PDNO intravenously, in contrast to inorganic nitrite intravenously, increased exhaled NO and counteracted pulmonary hypertension and vasodilated the systemic circulation, dose‐dependently, thereby showing efficient NO donation. Pulmonary embolization induced pulmonary hypertension and gas exchange disturbances. PDNO significantly decreased and normalized pulmonary vascular resistance and the right ventricle rate‐pressure product, without causing tolerance, with no significant side effects on the systemic circulation, nor on blood‐gas values or on methemoglobin formation. In conclusion, PDNO is a NO donor and an efficient vasodilator in the pulmonary circulation. Treatment with this or similar organic nitrites intravenously may be a future option to avoid right heart failure in life‐threatening acute pulmonary embolism.

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Hybrid silica-organic material with immobilized amino groups: surface probing and use for electrochemical determination of nitrite ions

Tkachenko

Rahim

Baraban

et al. 2013

J Sol-Gel Sci Technol

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Formation of new bioactive organic nitrites and their identification with gas chromatography–mass spectrometry and liquid chromatography coupled to nitrite reduction

Cited by 10 publications

References 37 publications

The novel nitric oxide donor PDNO attenuates ovine ischemia-reperfusion induced renal failure

The novel nitric oxide donor PDNO attenuates ovine ischemia-reperfusion induced renal failure

Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism

Hybrid silica-organic material with immobilized amino groups: surface probing and use for electrochemical determination of nitrite ions

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