Apple procyanidins induce hyperpolarization of rat aorta endothelial cells via activation of K+ channels

作者：Byun Eui Baek; Korematsu Sachiko; Ishikawa Teruaki; Nishizuka Taichi; Ohshima Shunji; Kanda Tomomasa; Matsui Toshiro^*

来源：Journal of Nutritional Biochemistry, 2012, 23(3): 278-286.

DOI：10.1016/j.jnutbio.2010.12.005

• Apple procyanidins
• Hyperpolarization
• K+ channel
• NO
• Proliferation

Apple procyanidins (AP), one of the polyphenol-rich compounds, showed an endothelial-dependent vasorelaxation in rat aorta, but the mechanisms of beneficial effects are still unclear. The present study was designed to clarify the potential role of AP in rat aorta endothelial cells (RAECs). The treatment of RAECs with AP (1-10 mu g/ml) resulted in a dose-dependent hyperpolarization with a maximum effect at 10 mu g/ml, and for this reason, AP (10 mu g/ml) was used in all the following experiments. AP-induced hyperpolarization was significantly inhibited by pretreatment of nonspecific K+ inhibitor, tetraethyl ammonium chloride or specific K+ channel inhibitors, iberiotoxin, glibenclamide, 4-aminopyridine and BaCl2, as well as by high KCI or Ca2+-free solution. AP-induced hyperpolarization was also proved using 64-channel multielectrode dish system that can monitor a direct and real-time change of membrane potential. Furthermore. AP treatment caused a significant increase of nitric oxide (NO) production and cyclic guanosine monophosphate levels via endothelial NO synthase messenger RNA expression. The NO production was inhibited by N-G-monoethyl-L-arginine or Ca2+-free solution and was completely abolished by their combination. Also, AP inhibited endothelial proliferation, while the effect was significantly abolished by N-G-monoethyl-L-arginine or tetraethyl ammonium chloride. These findings suggest that AP induces both hyperpolarization of RAECs via multiple activation of K+ channels and activation of NO/cyclic guanosine monophosphate pathway via increasing NO production or is responsible for antiangiogenic effect. Diminishment of hyperpolarization as well as NO production of AP in Ca2+-free solution implicated that AP would play a crucial role in promoting Ca2+ influx into endothelial cells so as to promote both actions. 2012 Elsevier Inc.

• 出版日期2012-3