title: Antioxidant activity and sex differences of acute vascular effects of amiodarone in advanced atherosclerosis.
abstract: Sexual dimorphisms of atherosclerosis and the susceptibility to arrhythmias and antiarrhythmic treatment have been reported. This study investigated acute effects of amiodarone on endothelium-dependent relaxation in the aorta of male and female apoE0 mice with advanced atherosclerosis. Amiodarone tissue uptake was quantified by high-performance liquid chromatography, and xanthine oxidase-dependent superoxide anion formation was investigated in vitro in presence or absence of amiodarone. Incubation with amiodarone for 30 min improved endothelium-dependent relaxation, which was associated with rapid vascular accumulation of amiodarone (P < 0.001) that was sex-dependent. In males, reduced endothelium-dependent relaxation was improved by amiodarone (from 88 +/- 3% to 100 +/- 2%, P < 0.01). Spontaneous phasic contractions, which were greater in females than in males (P < 0.001), were completely abolished by amiodarone (P < 0.0001). Amiodarone also inhibited generation of superoxide anion (P < 0.0001). These data show that amiodarone rapidly accumulates in atherosclerotic vascular tissue, abolishes vascular autorhythmicity, and improves endothelium-dependent function in atherosclerotic arteries. Antioxidant and vasodilator effects following amiodarone administration may contribute to its antiarrhythmic effects.
authors.affiliation: Department of Internal Medicine, Internal Medicine I, Medical Policlinic, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Traupe
authors.forename: Mario
authors.initials: M
authors.lastname: Keller
authors.forename: Eva
authors.initials: E
authors.lastname: Fojtu
authors.forename: Indranil
authors.initials: I
authors.lastname: Bhattacharya
authors.forename: Matthias
authors.initials: M
authors.lastname: Lang
authors.forename: Huy Riem
authors.initials: HR
authors.lastname: Ha
authors.forename: Wolfram
authors.initials: W
authors.lastname: Jochum
authors.forename: Alexa L
authors.initials: AL
authors.lastname: Mundy
authors.forename: Matthias
authors.initials: M
authors.lastname: Barton
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000638:Amiodarone / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D012737:Sex Factors; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D019820:Xanthine; D010656:Phenylephrine; D014969:Xanthine Oxidase; D000638:Amiodarone; D000109:Acetylcholine