Polyphenol-rich foods, such as fruits and vegetables, are protective against
cardiovascular diseases, but the mechanisms of the beneficial effects are still unknown. The goal of this research was to clarify actions of
procyanidin trimer (C1) in rat aortic endothelial cells (RAECs).
Procyanidin C1 at concentrations up to 50 μM was not cytotoxic to the RAECs. The addition of
procyanidin C1 to RAECs exerted a time-dependent hyperpolarization measured using a membrane potential-dependent
fluorescent probe, bis-(1,3-dibutylbarbituric acid) trimethine oxonol, whereas the hyperpolarization was significantly inhibited by the nonspecific K(+) channel inhibitor
tetraethylammonium chloride (
TEA). Moreover,
procyanidin C1 elevated intracellular Ca(2+) influx, which was totally abolished in the presence of Ca(2+)-free
solution with
EGTA.
Procyanidin C1 caused a significant increase in
nitric oxide (NO) production. The effect was significantly inhibited by an
NO synthase inhibitor, N(G)-monomethyl-
l-arginine, or
TEA. In conclusion, we demonstrated for the first time that
procyanidin C1 plays a potent role in promoting Ca(2+)-mediated signals such as the hyperpolarization via multiple K(+) channel activations and the NO release in RAECs, suggesting that
procyanidin C1 may represent novel and effective
therapy for the treatment of
cardiovascular diseases.