Jair Lozano-Cuenca¹, Oscar Alberto López-Canales², Ángel Miliar-García³, María de los Ángeles Martínez–Godínez³, Osiris Teran-Gallardo³, María Cristina Paredes-Carbajal², Ruth Mery López-Mayorga³, Enrique Fernando Castillo-Henkel³, Héctor Flores-Herrera⁴, Jorge Skiold López-Canales^{1, 3,}

The aim of this study was to gain further insights into the mechanisms responsible for the Val-Pro-Pro-induced vasodilation of rat aortic rings. The vasorelaxant effect was found at 10^-9-10^-4 M of the tripeptide on phenylephrine-precontracted rings. It was endothelium-dependent and concentration-dependent at the higher concentrations. The vasodilator response was not modified by preincubation with 3.1 x 10^-7 M glibenclamide, 10^-3 M 4-aminopyridine (4-AP), 10^-5 M indomethacin or 10^-5 M cycloheximide. However, this response was significantly diminished by preincubation with 10^-5 M L-NG-Nitroarginine methyl ester (L-NAME), 10^-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10^-6 M (9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i]benzodiazocine-10-carboxylic acid, methyl ester (KT 5823), 10^-2 M tetraethylammonium (TEA) and 10^-7 M apamin plus 10^-7 M charybdotoxin, as well as by the removal of the vascular endothelium. Apparently, Val-Pro-Pro directly produced vasorelaxation of phenylephrine-precontracted rat aortic rings by stimulating the vascular endothelium and activating the NO/cGMP/PKG/Ca²⁺-activated K⁺ channel pathway.

bioactive peptides, nitric oxide, potassium channels, rat aorta, vascular endothelium.