Oxidative stress and vascular function

Authors : Andreas DAİBER, Michael MADER, Paul STAMM, Elena ZİNßİUS, Swenja KRÖLLERSCHÖN, Matthias OELZE, Thomas MÜNZEL

Pages : 221-231

View : 12 | Download : 8

Publication Date : 2013-11-11

Article Type : Review Paper

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 insert ignore into journalissuearticles values(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 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 insert ignore into journalissuearticles values(mKATP);, the mitochondrial permeability transition pore insert ignore into journalissuearticles values(mPTP);, cSrc and protein kinases and the NADPH oxidase isoform Nox2 insert ignore into journalissuearticles values(and eventually Nox1);. This review will focus on the uncoupling of endothelial nitric oxide synthase insert ignore into journalissuearticles values(eNOS); by initially formed “kindling radicals” insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(BH4); will be highlighted as potential “redox switches” in eNOS. In addition, RONS-triggered increases in levels of asymmetric dimethylarginine insert ignore into journalissuearticles values(ADMA); and L-arginine depletion will be discussed as alternative reasons for dysfunctional eNOS. Finally, we present the clinical perspectives of eNOS uncoupling insert ignore into journalissuearticles values(and dysfunction); for the development and progression of cardiovascular disease and discuss the important prognostic value of the measurement of endothelial function insert ignore into journalissuearticles values(e.g. by flow-mediated dilation or forearm plethysmography); for patients with cardiovascular disease.
Keywords : Ion channels, cell biochemistry, biophysics, calcium signaling, cellular function, cellular physiology, metabolism, apoptosis, lipid peroxidation, nitric oxide synthase, ageing, antioxidants, neuropathy