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 μMin 1.0 μM 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 procya- nidins 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 μ, g/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 BaCl₂. These results indicate that procyanidin-induced vasorelaxation is associated with NO-cGMP pathway in combination with hyper- polarization due to multiple activation of Ca²⁺-dependent and -independent K ⁺ channels.