A procyanidin trimer, C1, promotes NO production in rat aortic endothelial cells via both hyperpolarization and PI3K/Akt pathways

Eui Baek Byun, Teruaki Ishikawa, Aki Suyama, Masaya Kono, Shohei Nakashima, Tomomasa Kanda, Takahisa Miyamoto, Toshiro Matsui

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Procyanidins, which are condensed catechins, have been elucidated as absorbable polyphenols, but their health-benefits remain unclear. The aim of this study was, thus, to clarify the efficacy and mechanism of each procyanidin oligomer in NO activation in rat aortic endothelial cells (RAECs). Treatment of RAECs with 50 μM procyanidin C1 (4β→8 trimer) resulted in a time- and dose-dependent hyperpolarization using the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, while no effect was observed for (-)-epicatechin (a monomer) and procyanidin B2 (4β→8 dimer). The C1-induced hyperpolarization was inhibited by iberiotoxin, a specific inhibitor of large-conductance Ca2-activated K+ (BKCa) channel, as well as 2-aminoethyl diphenylborinate (2-APB), a store-operated Ca2 entry inhibitor. Procyanidin C1 caused a significant increase in NO production from RAECs via phosphorylation of both eNOS and Akt, and the effect was completely inhibited by NG- monomethyl-l-arginine or combined treatment with iberiotoxin and the phosphatidylinositol 3-kinase (PI3K) specific inhibitor, wortmannin, as well as combined treatment with 2-APB and wortmannin. Taken together, these findings provide critical evidence that procyanidin C1, but not B2, has potential to induce NO production in RAECs via both Ca2-dependent BKCa channel-mediated hyperpolarization and Ca2-independent PI3K/Akt pathways.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalEuropean Journal of Pharmacology
Volume692
Issue number1-3
DOIs
Publication statusPublished - Oct 5 2012

All Science Journal Classification (ASJC) codes

  • Pharmacology

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