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

López-Canales JS, Lozano-Cuenca J, Muãoz-Islas E, Aguilar-Carrasco JC, López-Canales OA, López-Mayorga RM, Castillo-Henkel EF, Valencia-Hernández I, Castillo-Henkel C - Braz. J. Med. Biol. Res. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.

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.

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Related in: MedlinePlus

Concentration-dependent relaxation of 10-9-10-5 Mamfepramone (closed circles) and 10-9-10-5 Macetylcholine (open circles) in rat aortic rings with intact endothelium. Dataare reported as means±SE of n=6 observations. *P<0.05 vsbasal contraction (two-way ANOVA).
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f01: Concentration-dependent relaxation of 10-9-10-5 Mamfepramone (closed circles) and 10-9-10-5 Macetylcholine (open circles) in rat aortic rings with intact endothelium. Dataare reported as means±SE of n=6 observations. *P<0.05 vsbasal contraction (two-way ANOVA).

Mentions: Figure 1 shows the effects of the cumulativeaddition of 10-9-10-5 M amfepramone and10-9-10-5 M acetylcholine on intact rat aortic rings.Amfepramone and acetylcholine produced moderate concentration-dependentvasorelaxation in those aortic segments. The logEC50 values foramfepramone- and acetylcholine-induced vasorelaxation were -7.91 and -6.87 M,respectively. Following the addition of amfepramone and acetylcholine, the maximumvasorelaxation (Emax) was 17.34±3.66% and 48.98±8.75% of basalcontraction, respectively. The vasodilator response produced by amfepramone appearedimmediately on the addition of each concentration of this drug and reached a maximumvalue after 5 min. This vasodilator response was sustained and continued withoutchange.


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

López-Canales JS, Lozano-Cuenca J, Muãoz-Islas E, Aguilar-Carrasco JC, López-Canales OA, López-Mayorga RM, Castillo-Henkel EF, Valencia-Hernández I, Castillo-Henkel C - Braz. J. Med. Biol. Res. (2015)

Concentration-dependent relaxation of 10-9-10-5 Mamfepramone (closed circles) and 10-9-10-5 Macetylcholine (open circles) in rat aortic rings with intact endothelium. Dataare reported as means±SE of n=6 observations. *P<0.05 vsbasal contraction (two-way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4470313&req=5

f01: Concentration-dependent relaxation of 10-9-10-5 Mamfepramone (closed circles) and 10-9-10-5 Macetylcholine (open circles) in rat aortic rings with intact endothelium. Dataare reported as means±SE of n=6 observations. *P<0.05 vsbasal contraction (two-way ANOVA).
Mentions: Figure 1 shows the effects of the cumulativeaddition of 10-9-10-5 M amfepramone and10-9-10-5 M acetylcholine on intact rat aortic rings.Amfepramone and acetylcholine produced moderate concentration-dependentvasorelaxation in those aortic segments. The logEC50 values foramfepramone- and acetylcholine-induced vasorelaxation were -7.91 and -6.87 M,respectively. Following the addition of amfepramone and acetylcholine, the maximumvasorelaxation (Emax) was 17.34±3.66% and 48.98±8.75% of basalcontraction, respectively. The vasodilator response produced by amfepramone appearedimmediately on the addition of each concentration of this drug and reached a maximumvalue after 5 min. This vasodilator response was sustained and continued withoutchange.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Section of Postgraduate Studies and Investigation, Higher School of Medicine from the National Polytechnic Institute, Mexico City, Mexico.

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.

Show MeSH
Related in: MedlinePlus