Amiodarone causes endothelium-dependent vasodilation in human hand veins in vivo.
OBJECTIVE
Amiodarone, a class III antiarrhythmic agent, is a potent coronary vasodilator. However, direct evidence for its vasodilatory effects in human vasculature in vivo is not available. The aim of the study was to investigate the short-term effects of amiodarone in preconstricted human hand veins and to explore the underlying mechanisms.


METHODS
Thirty-one healthy male volunteers were studied with the use of the dorsal hand vein compliance technique. The hand veins of the subjects were preconstricted with the alpha 1-adrenergic receptor agonist phenylephrine, and amiodarone, inhibitors of nitric oxide formation (NG-monomethyl-L-arginine, L-NMMA), and adenosine triphosphate-dependent potassium channels (glyburide [INN, glibenclamide]) were infused in the presence or absence of a cyclooxygenase inhibitor (acetylsalicylic acid), and the venodilator effect was measured. Furthermore, amiodarone was infused in prostaglandin F2 alpha (dinoprost)-preconstricted hand veins.


RESULTS
Amiodarone produced dose-dependent venodilation (51% +/- 3% maximum). Maximum amiodarone-induced venodilation was lower in dinoprost compared with phenylephrine-preconstricted veins. Pretreatment with acetylsalicylic acid reduced the amiodarone-induced venodilation by 40% +/- 6%. L-NMMA reduced the amiodarone-induced venodilation after pretreatment with acetylsalicylic acid by 72% +/- 3%. Glyburide decreased the venodilatory response of amiodarone by 31% +/- 11%, whereas only a slight but not statistically significant additional reduction in venodilation was detected after pretreatment with acetylsalicylic acid. Infusion of the solvents of commercially available amiodarone (polysorbate 80 and benzyl alcohol) did not cause vasodilation in phenylephrine-preconstricted veins.


CONCLUSIONS
Amiodarone dilates preconstricted human hand veins in vivo and acts as a venodilator through the cyclooxygenase pathway, activation of nitric oxide synthase, and blockade of alpha adrenergic mechanisms.
Institute of Clinical Pharmacology, Faculty of Medicine, University of Technology, Dresden, Germany. mgrossma@rcs.urz.tu-dresden.de
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M
Grossman
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Dobrev
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W
Kirch
D000328:Adult; D000638:Amiodarone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006225:Hand / Q000098:blood supply*; D006801:Humans; D008297:Male; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D014665:Vasodilator Agents; D000638:Amiodarone