Antioxidant activity and sex differences of acute vascular effects of amiodarone in advanced atherosclerosis.
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.
Traupe
Tobias
T
Department of Internal Medicine, Internal Medicine I, Medical Policlinic, University Hospital Zürich, Zürich, Switzerland.
Keller
Mario
M
Fojtu
Eva
E
Bhattacharya
Indranil
I
Lang
Matthias
M
Ha
Huy Riem
HR
Jochum
Wolfram
W
Mundy
Alexa L
AL
Barton
Matthias
M
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
D000975:Antioxidants; D001057:Apolipoproteins E; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D019820:Xanthine; D010656:Phenylephrine; D014969:Xanthine Oxidase; D000638:Amiodarone; D000109:Acetylcholine