title: Procyanidin C1 causes vasorelaxation through activation of the endothelial NO/cGMP pathway in thoracic aortic rings.
abstract: The aim of this study was to clarify the efficacy of procyanidin C1 (Pro C1) for modulating vascular tone. Pro C1 induced a potent vasorelaxant effect on phenylephrine-constricted endothelium-intact thoracic aortic rings, but had no effect on denuded thoracic aortic rings. Moreover, Pro C1 caused a significant increase in nitric oxide (NO) production in endothelial cells. Pro C1-induced vasorelaxation and Pro C1-induced NO production were significantly decreased in the presence of a nonspecific potassium channel blocker (tetraethylammonium chloride [TEA]), an endothelial NO synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), and a store-operated calcium entry inhibitor (2-aminoethyl diphenylborinate [2-APB]). Pro C1-induced vasorelaxation was also completely abolished by an inhibitor of soluble guanyl cyclase, which suggests that the Pro C1 effects observed involved cyclic guanosine monophosphate (cGMP) production. Interestingly, Pro C1 significantly enhanced basal cGMP levels. Taken together, these results indicate that Pro C1-induced vasorelaxation is associated with the activation of the calcium-dependent NO/cGMP pathway, involving potassium channel activation. Thus, Pro C1 may represent a novel and potentially therapeutically relevant compound for the treatment of cardiovascular diseases.
authors: 1 Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute , Jeongeup, Korea.
authors: Eui-Baek
authors: EB
authors: Byun
authors: Nak-Yun
authors: NY
authors: Sung
authors: Mi-So
authors: MS
authors: Yang
authors: Du-Sup
authors: DS
authors: Song
authors: Eui-Hong
authors: EH
authors: Byun
authors: Jae-Kyung
authors: JK
authors: Kim
authors: Jong-Heum
authors: JH
authors: Park
authors: Beom-Seok
authors: BS
authors: Song
authors: Ju-Woon
authors: JW
authors: Lee
authors: Sang-Hyun
authors: SH
authors: Park
authors: Myung-Woo
authors: MW
authors: Byun
authors: Jae-Hun
authors: JH
authors: Kim
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D044946:Biflavonoids / Q000494:pharmacology*; D001896:Boron Compounds / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: C538758:2-aminoethyl diphenylborinate; D044946:Biflavonoids; D001896:Boron Compounds; D026902:Potassium Channel Blockers; D044945:Proanthocyanidins; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C479583:procyanidin C; D019789:Tetraethylammonium; D002392:Catechin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: K+ channel; NO/cGMP; procyanidin C1; store-operated Ca2+ entry; vasorelaxation