scholarly journals The Endothelin Receptor Antagonist Macitentan Improves Isosorbide-5-Mononitrate (ISMN) and Isosorbide Dinitrate (ISDN) Induced Endothelial Dysfunction, Oxidative Stress, and Vascular Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Sebastian Steven ◽  
Matthias Oelze ◽  
Michael Hausding ◽  
Siyer Roohani ◽  
Fatemeh Kashani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Endothelial Dysfunction ◽  
Receptor Antagonist ◽  
Isosorbide Dinitrate ◽  
Oxidative Burst ◽  
Organic Nitrates ◽  
Therapeutic Effects ◽  
Endothelin Receptor ◽  
Receptor Signaling

Objective. Organic nitrates such as isosorbide-5-mononitrate (ISMN) and isosorbide dinitrate (ISDN) are used for the treatment of patients with chronic symptomatic stable coronary artery disease and chronic congestive heart failure. Limiting side effects of these nitrovasodilators include nitrate tolerance and/or endothelial dysfunction mediated by oxidative stress. Here, we tested the therapeutic effects of the dual endothelin (ET) receptor antagonist macitentan in ISMN- and ISDN-treated animals. Methods and Results. Organic nitrates (ISMN, ISDN, and nitroglycerin (GTN)) augmented the oxidative burst and interleukin-6 release in cultured macrophages, whereas macitentan decreased the oxidative burst in isolated human leukocytes. Male C57BL/6j mice were treated with ISMN (75 mg/kg/d) or ISDN (25 mg/kg/d) via s.c. infusion for 7 days and some mice in addition with 30 mg/kg/d of macitentan (gavage, once daily). ISMN and ISDN in vivo therapy caused endothelial dysfunction but no nitrate (or cross-)tolerance to the organic nitrates, respectively. ISMN/ISDN increased blood nitrosative stress, vascular/cardiac oxidative stress via NOX-2 (fluorescence and chemiluminescence methods), ET1 expression, ET receptor signaling, and markers of inflammation (protein and mRNA level). ET receptor signaling blockade by macitentan normalized endothelial function, vascular/cardiac oxidative stress, and inflammatory phenotype in both nitrate therapy groups. Conclusion. ISMN/ISDN treatment caused activation of the NOX-2/ET receptor signaling axis leading to increased vascular oxidative stress and inflammation as well as endothelial dysfunction. Our study demonstrates for the first time that blockade of ET receptor signaling by the dual endothelin receptor blocker macitentan improves adverse side effects of the organic nitrates ISMN and ISDN.

scholarly journals Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Andreas Daiber ◽  
Matthias Oelze ◽  
Philip Wenzel ◽  
Franziska Bollmann ◽  
Andrea Pautz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Endothelial Dysfunction ◽  
Heme Oxygenase ◽  
Nitrate Tolerance ◽  
Heme Oxygenase 1 ◽  
Organic Nitrate ◽  
Organic Nitrates ◽  
Beneficial Effects ◽  
Vascular Oxidative Stress

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/–mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy.

scholarly journals Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model

2012 ◽  
Vol 72 (6) ◽  
pp. 600-605 ◽  
Author(s):  
Tatenobu Goto ◽  
Mohamed Hamed Hussein ◽  
Shin Kato ◽  
Ghada Abdel-Hamid Daoud ◽  
Takenori Kato ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Receptor Antagonist ◽  
Neonatal Sepsis ◽  
Endothelin Receptor Antagonist ◽  
Endothelin Receptor

scholarly journals Therapeutic Effects of Glycyrrhizic Acid

2013 ◽  
Vol 8 (3) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Lee Jia Ming ◽  
Adeline Chia Yoke Yin
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Side Effects ◽  
Herbal Medicine ◽  
Glycyrrhizic Acid ◽  
Glucuronic Acid ◽  
Glycyrrhetinic Acid ◽  
Therapeutic Effects ◽  
Wide Range ◽  
Anti Inflammatory

Glycyrrhizic acid (GA), belonging to a class of triterpenes, is a conjugate of two molecules, namely glucuronic acid and glycyrrhetinic acid. It is naturally extracted from the roots of licorice plants. With its more common uses in the confectionery and cosmetics industry, GA extends its applications as a herbal medicine for a wide range of ailments. At low appropriate doses, anti-inflammatory, anti-diabetic, antioxidant, anti-tumor, antimicrobial and anti-viral properties have been reported by researchers worldwide. This review summarizes the effects of GA on metabolic syndrome, tumorigenesis, microbes and viruses, oxidative stress, and inflammation, as well as the reported side effects of the drug.

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

Effects of empagliflozin on oxidative stress and endothelial dysfunction in STZ-induced Type 1 diabetic rat

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
M Oelze ◽  
S Kröller-Schön ◽  
M Mader ◽  
E Zinßius ◽  
P Stamm ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Diabetic Rat
Sign in / Sign up

Export Citation Format

Share Document