Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K⁺Channel Activations

Apple (Malus pumila) procyanidins led to a potent vasorelaxation effect in 1.0 microM phenylephrine-contractive rat thoracic aorta. Relaxation was greatly reduced by 70 mM KCl as well as by removal of the endothelium, suggesting that it was associated with endothelium-dependent hyperpolarization. Neither cAMP synthesis inhibition nor NAD(P)H oxidase inhibition abolished the effect. In contrast, complete abolition by a soluble guanylyl cyclase inhibitor revealed that apple procyanidins were mainly involved in the cGMP production pathways. In the presence of N(G)-monoethyl-L-arginine or tetraethylammonium chloride, the effect was still observed at higher concentrations (>25 microg/ml), while their combination completely diminished the effect. Vasorelaxation was to some extent affected by paxillin, apamin and glybenclamide, and was greatly affected by 4-aminopyridine and by BaCl(2). These results indicate that procyanidin-induced vasorelaxation is associated with NO-cGMP pathway in combination with hyperpolarization due to multiple activation of Ca(2+)-dependent and -independent K(+) channels.