scholarly journals Multitarget Antioxidant NO-Donor Organic Nitrates: A Novel Approach to Overcome Nitrates Tolerance, an Ex Vivo Study

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 166
Author(s):  
Elisabetta Marini ◽  
Marta Giorgis ◽  
Marta Leporati ◽  
Barbara Rolando ◽  
Konstantin Chegaev ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antioxidant Properties ◽  
Nitrate Tolerance ◽  
Organic Nitrates ◽  
Resistance Arteries ◽  
Aldehyde Dehydrogenase 2 ◽  
No Donor ◽  
Novel Approach ◽  
Ex Vivo Study ◽  
Chronic Use

Chronic use of glyceryl trinitrate (GTN) is limited by serious side effects, such as tolerance and endothelial dysfunction of coronary and resistance arteries. Although GTN is used as a drug since more than 130 years, the mechanisms of the vasodilatory effects and of tolerance development to organic nitrates are still incompletely elucidated. New synthesized organic nitrates with and without antioxidant properties were characterized for their ex vivo tolerance profile, in order to investigate the oxidative stress hypothesis of nitrate tolerance. The organic nitrates studied showed different vasodilation and tolerance profiles, probably due to the ability or inability of the compounds to interact with the aldehyde dehydrogenase-2 enzyme (ALDH-2) involved in bioactivation. Furthermore, nitrooxy derivatives endowed with antioxidant properties did not determine the onset of tolerance, even if bioactivated by ALDH-2. The results of this study could be further evidence of the involvement of ALDH-2 in the development of nitrate tolerance. Moreover, the behavior of organic nitrates with antioxidant properties supports the hypothesis of the involvement of ROS in inactivating ALDH-2.

scholarly journals Organic Nitrates and Nitrate Resistance in Diabetes: The Role of Vascular Dysfunction and Oxidative Stress with Emphasis on Antioxidant Properties of Pentaerithrityl Tetranitrate

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Matthias Oelze ◽  
Swenja Schuhmacher ◽  
Andreas Daiber
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Vascular Dysfunction ◽  
Antioxidant Properties ◽  
Nitrate Tolerance ◽  
Diabetic Patients ◽  
Organic Nitrates ◽  
Common Principle ◽  
No Bioavailability

Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by “NO” replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies.

The effect of peroxynitrite decomposition catalyst MnTBAP on aldehyde dehydrogenase-2 nitration by organic nitrates: Role in nitrate tolerance

2014 ◽  
Vol 89 ◽  
pp. 29-35 ◽  
Author(s):  
Vincenzo Mollace ◽  
Carolina Muscoli ◽  
Concetta Dagostino ◽  
Luigino Antonio Giancotti ◽  
Micaela Gliozzi ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Nitrate Tolerance ◽  
Organic Nitrates ◽  
Aldehyde Dehydrogenase 2

P6003Coronary artery spasm: a consequence of impaired nitric oxide/hydrogen sulphide signalling?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Liu ◽  
T H Nguyen ◽  
H Imam ◽  
T Heresztyn ◽  
I Stafford ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ex Vivo ◽  
Symptomatic Relief ◽  
Coronary Artery Spasm ◽  
In Vitro Studies ◽  
Aminooxyacetic Acid ◽  
Organic Nitrates ◽  
Platelet Response ◽  
No Donor

Abstract Background Coronary artery spasm (CAS) represents a major cause of patient morbidity, with variable clinical response to prophylaxis with calcium antagonists and generally poor symptomatic relief with organic nitrates. The precipitation of CAS with acetylcholine may reflect impaired nitric oxide (NO) release and/or signalling. We have recently demonstrated that platelets from patients with CAS exhibit markedly impaired anti-aggregatory responses to the NO donor sodium nitroprusside (SNP) (“NO resistance”). Purpose In the current experiments we sought to determine whether N-acetylcysteine (NAC), which is known to potentiate haemodynamic responses to organic nitrates, reverses NO resistance in platelets from CAS patients. Methods Patients with CAS were studied during acute (n=11) and chronic (n=24) phases of symptoms. NAC (10 g/24 hours) was infused together with low dose NTG (2.5 μg/min) in patients presenting with acute exacerbations, and platelets were studied ex vivo. In blood samples taken from chronic CAS patients, in vitro studies were performed to evaluate the possible role of H2S release (via cysteine formation) from NAC in putative potentiation of NO effect. Results (1) In acute patients, NTG/NAC infusion resulted in increases in platelet response to SNP (p=0.003); (2) In vitro studies showed that incubation with NAC or the H2S donor NaHS potentiated SNP responses (Figure 1A); (3) Effects of NAC were reversed by co-incubation with aminooxyacetic acid (AOAA) and D, L-propargylglycine (PAG), inhibitors of enzymatic cysteine bioconversion to release H2S (Figure 1B). Figure 1 Conclusion CAS-associated impairment of platelet NO signaling reflects a deficiency of the H2S/NO interaction, and can be reversed using exogenous H2S donors, including NAC.

Direct Visualization of A2, A3, and A4 Finger Flexor Pulley Injuries at 3-T and 7-T MRI: An Ex Vivo Study

2020 ◽  
Author(s):  
Rafael Heiss ◽  
Frank W. Roemer ◽  
Christoph Lutter ◽  
Rolf Janka ◽  
Volker Schöffl ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Direct Visualization ◽  
Ex Vivo Study

Impact of metal artefacts in QCT of the hip caused by a contralateral Gamma type nail: an ex vivo study

2014 ◽  
Author(s):  
Klaus Engelke ◽  
Nicolas Bouler ◽  
Oleg Museyko Fuerst ◽  
Sebastien Parratte ◽  
Thomas Fuerst ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Metal Artefacts ◽  
Ex Vivo Study

Interactions between programmable shunt valves and magnetically controlled growing rods for scoliosis

2020 ◽  
Vol 26 (6) ◽  
pp. 667-670
Author(s):  
Thomas Larrew ◽  
Mohammed Alshareef ◽  
Robert F. Murphy ◽  
Ramin Eskandari ◽  
Libby Kosnik Infinger
Keyword(s):  
Remote Control ◽  
Ex Vivo ◽  
Shunt Valve ◽  
Growing Rods ◽  
Growing Rod ◽  
Before And After ◽  
Magnetically Controlled Growing Rods ◽  
Ex Vivo Study

OBJECTIVEAlthough the advent of magnetic growing rod technology for scoliosis has provided a means to bypass multiple hardware lengthening operations, it is important to be aware that many of these same patients have a codiagnosis of hydrocephalus with magnet-sensitive programmable ventricular shunts. As the magnetic distraction of scoliosis rods has not previously been described to affect the shunt valve setting, the authors conducted an investigation to characterize the interaction between the two devices.METHODSIn this ex vivo study, the authors carried out 360 encounters between four different shunt valve types at varying distances from the magnetic external remote control (ERC) used to distract the growing rods. Valve settings were examined before and after every interaction with the remote control to determine if there was a change in the setting.RESULTSThe Medtronic Strata and Codman Hakim valves were found to have setting changes at distances of 3 and 6 inches but not at 12 inches. The Aesculap proGAV and Codman Certas valves, typically described as MRI-resistant, did not have any setting changes due to the magnetic ERC regardless of distance.CONCLUSIONSAlthough it is not necessary to check a shunt valve after every magnetic distraction of scoliosis growing rods, if there is concern that the magnetic ERC may have been within 12 inches (30 cm) of a programmable ventricular shunt valve, the valve should be checked at the bedside with a programmer or with a skull radiograph along with postdistraction scoliosis radiographs.

Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study)

2016 ◽  
Vol 16 (12) ◽  
pp. 1615-1621 ◽  
Author(s):  
Erik Andrade-Jorge ◽  
Marycarmen Godínez-Victoria ◽  
Luvia Enid Sánchez-Torres ◽  
Luis Humberto Fabila-Castillo ◽  
José G. Trujillo-Ferrara
Keyword(s):  
In Silico ◽  
Ex Vivo ◽  
Leukemia Cells ◽  
Ex Vivo Study ◽  
Murine Leukemia
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