Amiodarone acutely inhibits vascular activity of endothelin-converting enzymes

Endothelin has been implicated in arrhythmogenesis. Amiodarone, initially developed for the treatment of angina pectoris, is a potent inhibitor of ventricular arrhythmias. We investigated whether amiodarone (34 microg/mL) affects the vascular endothelin system of healthy Wistar-Kyoto rats. Contractility to big endothelin-1 and endothelin-1 was determined in aortic and carotid artery rings suspended in organ chambers. Functional activity of endothelin-converting enzymes was calculated for each concentration, and endothelin-converting enzyme-1 gene expression was analyzed using real-time polymerase chain reaction. Activity of functional endothelin-converting enzymes was sevenfold higher in the carotid artery than in the aorta (P < 0.001). Contractions to big endothelin-1 (0.1 micromol/L) were attenuated by amiodarone in the carotid artery (50 +/- 9% vs 90 +/- 8%, P < 0.01) but not in the aorta. Accordingly, contractility to endothelin-1 (0.1 micromol/L) was decreased by amiodarone in carotid rings only (105 +/- 7% vs 132 +/- 6%, P < 0.01). After acute exposure to amiodarone, functional activity of endothelin-converting enzymes at 0.1 micromol/L was slightly increased in the aorta (17 +/- 2% vs 11 +/- 2%, P < 0.05), but decreased in the carotid artery (40 +/- 9% vs 76 +/- 5%, P < 0.05). Endothelin-converting enzyme-1 mRNA expression in the aorta was not affected by amiodarone treatment. Thus, amiodarone acutely affects the activity of vascular endothelin-converting enzymes depending on the anatomical localization of the artery. Acute effects of amiodarone on endothelin-converting enzymes may contribute to its antiarrhythmic properties.