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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 (A) and 10-9-10-5 Macetylcholine (B) in 10-6 M phenylephrine (PE)precontracted rat aortic rings with (closed circles) and without (open circles)endothelium. Data are reported as means±SE of n=6 observations. *P<0.05vs basal phenylephrine-induced contraction; **P<0.05vs rings with endothelium (two-way ANOVA).
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f02: Concentration-dependent relaxation of 10-9-10-5 Mamfepramone (A) and 10-9-10-5 Macetylcholine (B) in 10-6 M phenylephrine (PE)precontracted rat aortic rings with (closed circles) and without (open circles)endothelium. Data are reported as means±SE of n=6 observations. *P<0.05vs basal phenylephrine-induced contraction; **P<0.05vs rings with endothelium (two-way ANOVA).

Mentions: Figure 2 shows the effects of the cumulativeaddition of 10-9-10-5 M amfepramone and10-9-10-5 M acetylcholine on phenylephrine-precontracted rataortic rings with and without endothelium. Amfepramone and acetylcholine elicited aconcentration-dependent relaxation on aortic rings with intact endothelium, an effectthat was blocked by the functional removal of the endothelium. The logEC50of amfepramone and acetylcholine for vasorelaxation in aortic rings with intactendothelium was -6.04 M and -7.67 M, respectively. The maximum vasorelaxationproduced by amfepramone and acetylcholine in aortic rings with intact endothelium was69.63±5.53% and 98.51±0.94%, respectively. The vasorelaxant response produced byamfepramone appeared immediately on the addition of each concentration of this drugand reached a maximum value after 15 min. This vasorelaxant response was sustainedand continued without change.


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 (A) and 10-9-10-5 Macetylcholine (B) in 10-6 M phenylephrine (PE)precontracted rat aortic rings with (closed circles) and without (open circles)endothelium. Data are reported as means±SE of n=6 observations. *P<0.05vs basal phenylephrine-induced contraction; **P<0.05vs rings with endothelium (two-way ANOVA).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f02: Concentration-dependent relaxation of 10-9-10-5 Mamfepramone (A) and 10-9-10-5 Macetylcholine (B) in 10-6 M phenylephrine (PE)precontracted rat aortic rings with (closed circles) and without (open circles)endothelium. Data are reported as means±SE of n=6 observations. *P<0.05vs basal phenylephrine-induced contraction; **P<0.05vs rings with endothelium (two-way ANOVA).
Mentions: Figure 2 shows the effects of the cumulativeaddition of 10-9-10-5 M amfepramone and10-9-10-5 M acetylcholine on phenylephrine-precontracted rataortic rings with and without endothelium. Amfepramone and acetylcholine elicited aconcentration-dependent relaxation on aortic rings with intact endothelium, an effectthat was blocked by the functional removal of the endothelium. The logEC50of amfepramone and acetylcholine for vasorelaxation in aortic rings with intactendothelium was -6.04 M and -7.67 M, respectively. The maximum vasorelaxationproduced by amfepramone and acetylcholine in aortic rings with intact endothelium was69.63±5.53% and 98.51±0.94%, respectively. The vasorelaxant response produced byamfepramone appeared immediately on the addition of each concentration of this drugand reached a maximum value after 15 min. This vasorelaxant response was sustainedand continued without change.

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