Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings

• Published in: Brazilian journal of medical and biological research Vol. 48; no. 6; pp. 537 - 544
• Main Authors: López-Canales, J S, Lozano-Cuenca, J, Muãoz-Islas, E, Aguilar-Carrasco, J C, López-Canales, O A, López-Mayorga, R M, Castillo-Henkel, E F, Valencia-Hernández, I, Castillo-Henkel, C
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01-06-2015; Associação Brasileira de Divulgação Científica
• Subjects: Acetylcholine - pharmacology; Amfepramone; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Appetite Depressants - pharmacology; BIOLOGY; Biomedical Sciences; Calcium Channels - drug effects; Calcium Channels - metabolism; Cardiovascular pharmacology; Diethylpropion; Diethylpropion - pharmacology; Dosage and administration; Drug therapy; Endothelium, Vascular - drug effects; Male; MEDICINE, RESEARCH & EXPERIMENTAL; NG-Nitroarginine Methyl Ester - metabolism; Nitric oxide; Nitric Oxide Synthase Type III - drug effects; Obesity; Phenylephrine - pharmacology; Potassium channels; Potassium Channels - drug effects; Potassium Channels - metabolism; Rat aorta; Rats, Wistar; Tetraethylammonium - metabolism; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Vasodilator Agents - pharmacology; Brazil; Rat aorta; Obesity; Cardiovascular pharmacology; Amfepramone; Potassium channels; Nitric oxide
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X20144261

Amfepramone (diethylpropion) is an appetite-suppressant drug used for the treatment of overweight and obesity. It has been suggested that the systemic and central activity of amfepramone produces cardiovascular effects such as transient ischemic attacks and primary pulmonary hypertension. However, it is not known whether amfepramone produces immediate vascular effects when applied in vitro to rat aortic rings and, if so, what mechanisms may be involved. We analyzed the effect of amfepramone on phenylephrine-precontracted rat aortic rings with or without endothelium and the influence of inhibitors or blockers on this effect. Amfepramone produced a concentration-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings that was not affected by the vehicle, atropine, 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. The vasorelaxant effect of amfepramone was significantly attenuated by NG-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA), and was blocked by removal of the vascular endothelium. These results suggest that amfepramone had a direct vasorelaxant effect on phenylephrine-precontracted rat aortic rings, and that inhibition of endothelial nitric oxide synthase and the opening of Ca2+-activated K+ channels were involved in this effect.