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.
Matsui
Toshiro
T
Division of Bioresources and Biosciences, Faculty of Agriculture, Graduate School of Kyushu University, Fukuoka, Japan. tmatsui@agr.kyushu-u.ac.jp
Korematsu
Sachiko
S
Byun
Eui-Baek
EB
Nishizuka
Taichi
T
Ohshima
Shunji
S
Kanda
Tomomasa
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D027845:Malus / Q000737:chemistry*; D008564:Membrane Potentials / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000975:Antioxidants; D044946:Biflavonoids; D015221:Potassium Channels; D044945:Proanthocyanidins; D009569:Nitric Oxide; C017674:procyanidin; D002392:Catechin; D006152:Cyclic GMP