TY - JOUR
T1 - Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria-style diet
AU - López-Canales, Jorge Skiold
AU - Lozano-Cuenca, Jair
AU - López-Canales, Oscar Alberto
AU - Aguilar-Carrasco, José Carlos
AU - Aranda-Zepeda, Lidia
AU - López-Sánchez, Pedro
AU - Castillo-Henkel, Enrique Fernando
AU - López-Mayorga, Ruth Mery
AU - Valencia-Hernández, Ignacio
N1 - Publisher Copyright:
© 2015 Wiley Publishing Asia Pty Ltd.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a semi-solid, cafeteria-style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine-precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10-9-10-5-mol/L rosuvastatin produced lower concentration-dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10-5-mol/L NG-nitro-l-arginine methyl ester, 10-2-mol/L tetraethylammonium, 10-3-mol/L 4-aminopyridine, 10-7-mol/L apamin plus 10-7-mol/L charybdotoxin, 10-5-mol/L indomethacin, or 10-5-mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca2+-activated and voltage-activated K+ channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect.
AB - The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a semi-solid, cafeteria-style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine-precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10-9-10-5-mol/L rosuvastatin produced lower concentration-dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10-5-mol/L NG-nitro-l-arginine methyl ester, 10-2-mol/L tetraethylammonium, 10-3-mol/L 4-aminopyridine, 10-7-mol/L apamin plus 10-7-mol/L charybdotoxin, 10-5-mol/L indomethacin, or 10-5-mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca2+-activated and voltage-activated K+ channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect.
KW - Aorta
KW - Endothelium
KW - Obesity
KW - Rate
KW - Rosuvastatin
UR - http://www.scopus.com/inward/record.url?scp=84930341930&partnerID=8YFLogxK
U2 - 10.1111/1440-1681.12406
DO - 10.1111/1440-1681.12406
M3 - Artículo
C2 - 25881486
SN - 0305-1870
VL - 42
SP - 653
EP - 661
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 6
ER -