title: Aminoethyl nitrate--the novel super nitrate?
abstract: Long-term use of most organic nitrates is limited by development of tolerance, induction of oxidative stress and endothelial dysfunction. In this issue of the BJP, Schuhmacher et al. characterized a novel class of organic nitrates with amino moieties (aminoalkyl nitrates). Aminoethyl nitrate was identified as a novel organic mononitrate with high potency but devoid of induction of mitochondrial oxidative stress. Cross-tolerance to nitroglycerin or the endothelium-dependent agonist acetylcholine after in vivo treatment was not observed. Like all nitrates, aminoethyl nitrate induced vasorelaxation by activation of soluble guanylate cyclase. Thus, in contrast to the prevailing view, high potency in an organic nitrate is not necessarily accompanied by induction of oxidative stress or endothelial dysfunction. This work from Daiber's group is an important step forward in the understanding of nitrate bioactivation, tolerance phenomena and towards the development of better organic nitrates for clinical use.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum, Julius-Maximilians-Universität Würzburg, Würzburg, Germany. j.bauersachs@medizin.uni-wuerzburg.de
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D004361:Drug Tolerance; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009566:Nitrates / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009566:Nitrates; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D005996:Nitroglycerin; D000109:Acetylcholine; C546031:aminoethyl nitrate