[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.


CONCLUSIONS
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.
Rodrigues
Alfredo José
AJ
Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP. alfredo@smnp.usp.br
Evora
Paulo Roberto Barbosa
PR
Maruo
Ayako
A
Schaff
Hartzell V
HV
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005079:Excipients / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D011136:Polysorbates / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D005079:Excipients; D011136:Polysorbates; D019335:Nitroarginine; D000638:Amiodarone; D007213:Indomethacin