[Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries].

OBJECTIVE To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of polysorbate 80, amiodarone dissolved in water, amiodarone dissolved in polysorbate 80, and a commercial presentation of amiodarone (Cordarone). The experiments were conducted in the presence of the following enzymatic blockers: only indomethacin, Nomega-nitro-L-arginine associated with indomethacin, and only Nomega-nitro-L-arginine. RESULTS Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation. Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate 80 caused endothelium-dependent relaxation, which was greater for amiodarone dissolved in polysorbate and for Cordarone. Only the association of indomethacin and Nomega-nitro-L-arginine could eliminate the endothelium-dependent relaxation caused by amiodarone dissolved in polysorbate 80. CONCLUSION The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.

[1]  S. Connolly,et al.  Long-term amiodarone therapy and the risk of complications after cardiac surgery: results from the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT). , 2003, The Journal of thoracic and cardiovascular surgery.

[2]  C. Haffajee,et al.  Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia. , 2002, The American journal of cardiology.

[3]  T. Holman,et al.  Inhibition studies of soybean and human 15-lipoxygenases with long-chain alkenyl sulfate substrates. , 2001, Biochemistry.

[4]  D. Dobrev,et al.  N-desethylamiodarone modulates intracellular calcium concentration in endothelial cells , 2000, Naunyn-Schmiedeberg's Archives of Pharmacology.

[5]  D. Nisato,et al.  Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction. , 2000, Journal of cardiovascular pharmacology.

[6]  J. J. Moreno.  Arachidonic acid release and prostaglandin E2 synthesis as irritant index of surfactants in 3T6 fibroblast cultures. , 2000, Toxicology.

[7]  T. Horie,et al.  Non-ionic detergent Tween 80 modulates VP-16 resistance in classical multidrug resistant K562 cells via enhancement of VP-16 influx. , 2000, Cancer letters.

[8]  W. Kirch,et al.  Local venous response to N‐desethylamiodarone in humans , 2000, Clinical pharmacology and therapeutics.

[9]  C. J. Thoman.  The versatility of polysorbate 80 (Tween 80) as an ionophore. , 1999, Journal of pharmaceutical sciences.

[10]  W. Lehmann,et al.  Arachidonic acid metabolism in primary irritant dermatitis produced by patch testing of human skin with surfactants. , 1998, Toxicology and applied pharmacology.

[11]  W. Kirch,et al.  Amiodarone causes endothelium‐dependent vasodilation in human hand veins in vivo * , 1998, Clinical pharmacology and therapeutics.

[12]  M. Oz,et al.  Refractory vasodilation after cardiopulmonary bypass for heart transplantation in recipients on combined amiodarone and angiotensin-converting enzyme inhibitor therapy: a role for vasopressin administration. , 1998, Journal of cardiothoracic and vascular anesthesia.

[13]  K. Kamiya,et al.  Cellular electropharmacology of amiodarone. , 1997, Cardiovascular research.

[14]  P. Korkusuz,et al.  Tween 80 and endothelium: functional reduction due to tissue damage. , 1996, Research communications in molecular pathology and pharmacology.

[15]  U. Hodoğlugil,et al.  Effects of polysorbates and Cremophor EL on vascular responses in rat aorta , 1995, Experientia.

[16]  R. Seifert,et al.  The class III antiarrhythmic drug amiodarone directly activates pertussis toxin-sensitive G proteins. , 1995, Molecular pharmacology.

[17]  J. Giacomini,et al.  Antiarrhythmic agent amiodarone possesses calcium channel blocker properties. , 1994, Journal of cardiovascular pharmacology.

[18]  R. Bache,et al.  Effects of Amiodarone With and Without Polysorbate 80 on Myocardial Oxygen Consumption and Coronary Blood Flow During Treadmill Exercise in the Dog , 1991, Journal of cardiovascular pharmacology.

[19]  G. Powis,et al.  Amiodarone-mediated increase in intracellular free Ca2+ associated with cellular injury to human pulmonary artery endothelial cells. , 1990, Toxicology and applied pharmacology.

[20]  R. Grolleau,et al.  A randomized hemodynamic comparison of intravenous amiodarone with and without Tween 80. , 1988, European heart journal.

[21]  C. J. Thoman.  Ionophoric properties of polysorbate 80. , 1986, Journal of pharmaceutical sciences.

[22]  S. Teasdale,et al.  Anaesthesia and amiodarone , 1985, Canadian Anaesthetists' Society journal.

[23]  E. Masini,et al.  Histamine-releasing properties of Polysorbate 80in vitro andin vivo: correlation with its hypotensive action in the dog , 1985, Agents and Actions.

[24]  Bramahn . Singh,et al.  Amiodarone: historical development and pharmacologic profile. , 1983, American heart journal.

[25]  N. El-Sherif,et al.  Hypotensive Action of Commercial Intravenous Amiodarone and Polysorbate 80 in Dogs , 1982, Journal of cardiovascular pharmacology.

[26]  P. Kowey,et al.  Intravenous amiodarone. , 1997, Journal of the American College of Cardiology.

[27]  T. Horie,et al.  Effect of Tween-80 on cell killing by etoposide in human lung adenocarcinoma cells , 1999, Cancer Chemotherapy and Pharmacology.

[28]  L. Heppel,et al.  Methods for rapidly altering the permeability of mammalian cells. , 1977, Journal of supramolecular structure.