title: Mechanisms involved in the vasorelaxant effects produced by the acute application of amfepramone in vitro to rat aortic rings.
abstract: 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.
authors.affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: J S
authors.initials: JS
authors.lastname: López-Canales
authors.affiliation: Department of Cellular Biology, National Institute of Perinatology, Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Lozano-Cuenca
authors.affiliation: Department of Cellular Biology, National Institute of Perinatology, Mexico City, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Muãoz-Islas
authors.affiliation: Department of Cellular Biology, National Institute of Perinatology, Mexico City, Mexico.
authors.forename: J C
authors.initials: JC
authors.lastname: Aguilar-Carrasco
authors.affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: O A
authors.initials: OA
authors.lastname: López-Canales
authors.affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: R M
authors.initials: RM
authors.lastname: López-Mayorga
authors.affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: E F
authors.initials: EF
authors.lastname: Castillo-Henkel
authors.affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Valencia-Hernández
authors.affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Castillo-Henkel
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001067:Appetite Depressants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004053:Diethylpropion / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001067:Appetite Depressants; D015220:Calcium Channels; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019789:Tetraethylammonium; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D004053:Diethylpropion; D019331:NG-Nitroarginine Methyl Ester
references.citation: Annu Rev Pharmacol Toxicol. 1984;24:175-97
references.pmid: 6203480
references.citation: Hypertension. 1986 Apr;8(4):344-8
references.pmid: 2870025
references.citation: IDrugs. 2003 Jun;6(6):566-72
references.pmid: 12811679
references.citation: Blood Vessels. 1990;27(2-5):238-45
references.pmid: 2242444
references.citation: Arch Kriminol. 2013 Mar-Apr;231(3-4):116-29
references.pmid: 23678625
references.citation: Br J Pharmacol. 1994 Jun;112(2):519-24
references.pmid: 8075871
references.citation: Circ Res. 1983 Nov;53(5):557-73
references.pmid: 6313250
references.citation: Funct Neurol. 1993 Sep-Oct;8(5):351-4
references.pmid: 8144062
references.citation: Braz J Med Biol Res. 2011 May;44(5):438-44
references.pmid: 21445535
references.citation: Biochem Biophys Res Commun. 1989 Dec 15;165(2):802-9
references.pmid: 2480784
references.citation: Am J Physiol Heart Circ Physiol. 2011 May;300(5):H1602-8
references.pmid: 21335473
references.citation: J Vet Pharmacol Ther. 2008 Feb;31(1):1-8
references.pmid: 18177312
references.citation: Biophys J. 1994 Dec;67(6):2316-25
references.pmid: 7696472
references.citation: Diabetes Care. 2011 May;34 Suppl 2:S114-9
references.pmid: 21525441
references.citation: Biochem Biophys Res Commun. 1987 Jul 15;146(1):21-5
references.pmid: 2440431
references.citation: Indian J Exp Biol. 2012 Dec;50(12):883-8
references.pmid: 23986972
references.citation: J Pharm Pharmacol. 1977 May;29(5):318-9
references.pmid: 17704
references.citation: Cancer Res. 1993 Jun 1;53(11):2548-52
references.pmid: 8495418
references.citation: Eur Respir J. 2003 Sep;22(3):560-2
references.pmid: 14516151
references.citation: Prostaglandins. 1979 Apr;17(4):573-80
references.pmid: 379918
references.citation: Nature. 1980 Nov 27;288(5789):373-6
references.pmid: 6253831
references.citation: Curr Opin Cardiol. 2002 Sep;17(5):486-92
references.pmid: 12357124
references.citation: Br J Pharmacol. 1988 Dec;95(4):1165-74
references.pmid: 2851359
references.citation: Physiologie. 1978 Apr-Jun;15(2):117-25
references.pmid: 97686
references.citation: BMJ Clin Evid. 2011;2011. pii: 0604
references.pmid: 21411021
references.citation: Gen Pharmacol. 1998 Jan;30(1):13-24
references.pmid: 9457476
references.citation: Br J Pharmacol Chemother. 1963 Oct;21:285-94
references.pmid: 14081659
references.citation: Clin Psychopharmacol Neurosci. 2013 Apr;11(1):7-12
references.pmid: 23678348
references.citation: Arch Mal Coeur Vaiss. 1999 Sep;92(9):1213-9
references.pmid: 10533670
references.citation: J Physiol. 1994 Dec 1;481 ( Pt 2):407-14
references.pmid: 7738833
references.citation: Br J Pharmacol. 1990 Jul;100(3):427-34
references.pmid: 2167732
references.citation: Eur J Biochem. 1977 Feb 15;73(1):287-96
references.pmid: 837942
references.citation: Nat New Biol. 1971 Jun 23;231(25):232-5
references.pmid: 5284360
references.citation: J Cardiovasc Pharmacol. 1984;6 Suppl 2:S336-43
references.pmid: 6206342
references.citation: J Pharmacol Exp Ther. 2012 Jun;341(3):756-63
references.pmid: 22427701
references.citation: Toxicol Appl Pharmacol. 2003 Jul 15;190(2):170-6
references.pmid: 12878046
references.citation: Clin Sci Mol Med Suppl. 1978 Dec;4:195s-198s
references.pmid: 365431
references.citation: G Ital Cardiol (Rome). 2008 Apr;9(4 Suppl 1):83S-93S
references.pmid: 18773755
references.citation: Drug Saf. 2011 Aug 1;34(8):641-50
references.pmid: 21751825