胺碘酮在人体内可引起手部静脉的内皮依赖性血管舒张。

Amiodarone causes endothelium-dependent vasodilation in human hand veins in vivo.

作者信息

Grossman M, Dobrev D, Kirch W

机构信息

Institute of Clinical Pharmacology, Faculty of Medicine, University of Technology, Dresden, Germany.

出版信息

Clin Pharmacol Ther. 1998 Sep;64(3):302-11. doi: 10.1016/S0009-9236(98)90179-5.

DOI:10.1016/S0009-9236(98)90179-5

PMID:9757154

Abstract

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.

摘要

目的

胺碘酮是一种Ⅲ类抗心律失常药物，也是一种强效的冠状动脉血管扩张剂。然而，其在人体血管系统中的血管舒张作用尚无直接证据。本研究旨在探讨胺碘酮对预先收缩的人手部静脉的短期影响，并探究其潜在机制。

方法

采用手背静脉顺应性技术对31名健康男性志愿者进行研究。受试者的手部静脉用α1 -肾上腺素能受体激动剂去氧肾上腺素预先收缩，在存在或不存在环氧化酶抑制剂（阿司匹林）的情况下，输注胺碘酮、一氧化氮生成抑制剂（N-甲基-L-精氨酸，L-NMMA）和三磷酸腺苷依赖性钾通道阻滞剂（格列本脲），并测量静脉舒张效果。此外，在前列腺素F2α（地诺前列素）预先收缩的手部静脉中输注胺碘酮。

结果

胺碘酮产生剂量依赖性静脉舒张（最大舒张率为51%±3%）。与去氧肾上腺素预先收缩的静脉相比，地诺前列素预先收缩的静脉中胺碘酮诱导的最大静脉舒张率较低。阿司匹林预处理使胺碘酮诱导的静脉舒张降低40%±6%。L-NMMA在阿司匹林预处理后使胺碘酮诱导的静脉舒张降低72%±3%。格列本脲使胺碘酮的静脉舒张反应降低31%±11%，而在阿司匹林预处理后，仅检测到静脉舒张有轻微但无统计学意义的进一步降低。输注市售胺碘酮的溶剂（聚山梨酯80和苯甲醇）在去氧肾上腺素预先收缩的静脉中未引起血管舒张。