cyclic-gmp and procyanidin

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.

Topics: Animals; Antioxidants; Aorta, Thoracic; Biflavonoids; Catechin; Cyclic GMP; In Vitro Techniques; Male; Malus; Membrane Potentials; Nitric Oxide; Potassium Channels; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Signal Transduction; Vasodilation

The extract of Crataegus, a mixture of flavonoids and procyanidins extracted from hawthorn, Crataegus oxyacantha, L. and C. monogyna Jacq., relaxed vascular tone or increased production of cyclic GMP in the rat aorta, but flavonoid components of Crataegus extract, hyperoside, rutin and vitexin, did not affect the vascular tone. The aim of the present study was to characterize the endothelium-dependent relaxation elicited by procyanidins fractionated from Crataegus extract in isolated rat aorta. Procyanidins caused endothelium-dependent relaxation which was associated with the production of cyclic GMP. Both responses to these procyanidins were inhibited by methylene blue or N(G)-nitro-L-arginine, but not by indomethacin. Relaxation in response to procyanidins was not affected by atropine, diphenhydramine, [D-Pro2,D-Trp7,9]substance P, propranolol, nifedipine, verapamil and glibenclamide, but were markedly reduced by tetraethylammonium. These findings showed that procyanidins in Crataegus extract may be responsible for the endothelium-dependent nitric oxide-mediated relaxation in isolated rat aorta, possibly via activation of tetraethylammonium-sensitive K+ channels.

Topics: Animals; Aorta; Biflavonoids; Calcium Channel Blockers; Catechin; Crataegus; Cyclic GMP; Drug Interactions; Endothelium, Vascular; Male; Nitric Oxide; Plant Extracts; Potassium Channel Blockers; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Tetraethylammonium; Vasodilation