Oxidative stress and vascular function

Cell Membranes and Free Radical Research Volume 5, Number 1, 2013 ISSN Numbers: 1308-4178 (On-line), 1308-416X Indexing: Google Scholar, Index Copernicus, Chemical Abstracts, Scopus (Elsevier), EBSCOhost Research Database EDITOR Editor in Chief Mustafa Nazıroğlu, Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey. Phone: +90 246 211 37 08. Fax:+90 246 237 11 65 E-mail: Managing Editor A. Cihangir Uğuz, Department of Biophysics, Medical Faculty, Suleyman Demirel University, Isparta, Turkey. E-mail: EDITORIAL BOARD Cell Membranes, Ion Channels and Calcium Signaling Alexei Tepikin, The Physiological Laboratory, University of Liverpool, Liverpool, UK Andreas Lückhoff, Institute of Physiology, Medical Faculty, RWTH-Aachen University, Germany Andreas Daiber, 2nd Medical Clinic, Molecular Cardiology, Medical Center of the Johannes Gutenberg University , Mainz, Germany Giorgio Aicardi, Department of Human and General Physiology, University of Bologna, Italy. Gemma A. Figtree, North Shore Heart Research Group Kolling Institute of Medical Research University of Sydney and Royal North Shore Hospital Sydney, AUSTRALIA. Jose Antonio Pariente, Department of Physiology, University of Extremadura, Badajoz, Spain. James W. Putney, Jr. Laboratory of Signal Transduction, NIEHS, NC, USA. Martyn Mahaut Smith, Department of Cell Physiology and Pharmacology, Universtiy of Leicester, Leicester, UK. Stephan M. Huber, Department of Radiation Oncology, Eberhard - Karls University Tubingen, Germany Enzymatic Antioxidants Michael Davies, Deputy Director, The Heart Research Institute, Sydney, Australia. Süleyman Kaplan, Department of Histology and Embryology, Medical Faculty, Samsun, Turkey Xingen G. Lei, Molecular Nutrition, Department of Animal Science, Cornell University, Ithaca, NY, USA Ozcan Erel, Department of Biochemistry, Medical Faculty, Yıldırım Beyazıt University. Nonenzymatic Antioxidants, Nutrition and Melatonin Ana B. Rodriguez Moratinos, Department of Physiology, University of Extremadura, Badajoz, Spain. Cem Ekmekcioglu, Department of Physiology, Faculty of Medical University of Vienna, Austria. Peter J. Butterworth, Nutritional Sciences Division, King’s College London, London, UK ii Cell Membranes and Free Radical Research AIM AND SCOPES Cell Membranes and Free Radical Research is a print and online journal that publishes original research articles, reviews and short reviews on the molecular basis of biophysical, physiological and pharmacological processes that regulate cellular function, and the control or alteration of these processes by the action of receptors, neurotransmitters, second messengers, cation, anions, drugs or disease. Areas of particular interest are four topics. They are; A- Ion Channels (Na+ - K+ Channels, Cl – channels, Ca2+ channels, ADP-Ribose and metabolism of NAD+, PatchClamp applications) B- Oxidative Stress (Antioxidant vitamins, antioxidant enzymes, metabolism of nitric oxide, oxidative stress, biophysics, biochemistry and physiology of free oxygen radicals C- Interaction Between Oxidative Stress and Ion Channels (Effects of the oxidative stress on the activation of the voltage sensitive cation channels, effect of ADP-Ribose and NAD+ on activation of the cation channels which are sensitive to voltage, effect of the oxidative stress on activation of the TRP channels) D- Gene and Oxidative Stress (Gene abnormalities. Interaction between gene and free radicals. Gene anomalies and iron. Role of radiation and cancer on gene polymorphism) READERSHIP Biophysics Biochemistry Biology Biomedical Engineering Pharmacology Physiology Genetics Cardiology Neurology Oncology Psychiatry Neuroscience Keywords Ion channels, cell biochemistry, biophysics, calcium signaling, cellular function, cellular physiology, metabolism, apoptosis, lipid peroxidation, nitric oxide synthase, ageing, antioxidants, neuropathy. Volume 5, Number 1, 2013 Oxidative Stress and Vascular Function Andreas Daiber, Michael Mader, Paul Stamm, Elena Zinßius, Swenja Kröller-Schön, Matthias Oelze, Thomas Münzel From the 2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany List of abbreviations RONS reactive oxygen or nitrogen species mPTP mitochondrial permeability transition pore NOX1 NOX2 eNOS Abstract Many drug-induced complications and diseases are known to be associated with or even based on a dysequilibrium between the formation of reactive oxygen or nitrogen species (RONS) and the expression/activity of antioxidant enzymes that catalyze the breakdown of these harmful reactive species. The “kindling radical” concept is based on the initial formation of RONS that in Corresponding Address Prof. Dr. Andreas Daiber, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, II. Medizinische Klinik – Labor für Molekulare Kadiologie, Gebäude 605, Langenbeckstr. 1, 55131 Mainz, Germany, Phone: +49 (0)6131 176280, Fax: +49 (0)6131 176293, E-mail: turn activate additional sources of RONS in certain pathological conditions. Recently, we and others have demonstrated such “cross-talk” between NADPH oxidases and mitochondria in the setting of nitroglycerin-induced nitrate tolerance, the aging process and angiotensin-II triggered arterial hypertension via redox pathways compromising the mitochondrial, ATP-sensitive potassium channel (mKATP), the mitochondrial permeability transition pore (mPTP), cSrc and protein kinases and the NADPH oxidase isoform Nox2 (and eventually Nox1). This review will focus on the uncoupling of endothelial nitric oxide synthase (eNOS) by initially formed “kindling radicals” (RONS) and on the different “redox switches” that are involved in the uncoupling process of eNOS. S-glutathionylation of the eNOS reductase domain, adverse phosphorylation of eNOS, and of course the oxidative depletion of tetrahydrobiopterin (BH4) will be highlighted as potential “redox switches” in eNOS. In addition, RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) and L-arginine depletion will be discussed as alternative reasons for dysfunctional eNOS. Finally, we present the clinical perspectives of eNOS uncoupling (and dysfunction) for the development and progression of cardiovascular disease and discuss the important prognostic value of the measurement of endothelial function (e.g. by flow-mediated dilation or forearm plethysmography) for patients with cardiovascular disease. Keywords Oxidative stress, superoxide, peroxynitrite, nitric oxide synthase uncoupling, NADPH oxidase, mitochondria, xanthine oxidase. Cell Membranes and Free Radical Research Volume 5, Number 1, 2013 221 Oxidative stress and vascular function Introduction Oxidative stress has been demonstrated to be a hallmark of most cardiovascular and neurodegenerative diseases (Griendling and FitzGerald 2003; Ischiropoulos and Beckman 2003). The most common reactive oxygen and nitrogen species (RONS) include s (...truncated)