Abstract

The present study investigated the involvement of endothelial nitric oxide in relaxation induced by purified green tea (-)epicatechin in rat isolated mesenteric arteries. (-)Epicatechin caused both endothelium-dependent and -independent relaxation. NG-Nitro-L-arginine methyl ester (L-NAME, 100 microM) and methylene blue (10 microM) significantly attenuated (-)epicatechin-induced relaxation in endothelium-intact tissues. L-Arginine (1 mM) partially antagonized the effect of L-NAME. (-)Epicatechin-induced relaxation was inhibited by Rp-guanosine 3',5'-cyclic monophosphothioate triethylamine. In contrast, indomethacin and glibenclamide had no effect. (-)Epicatechin (100 microM) significantly increased the tissue content of cyclic GMP and NG-nitro-L-arginine (100 microM) or removal of the endothelium abolished this increase. (-)Epicatechin (100 microM) induced an increase in intracellular Ca2+ levels in cultured human umbilical vein endothelial cells. Iberiotoxin at 100 nM attenuated (-)epicatechin-induced relaxation in endothelium-intact arteries and this effect was absent in the presence of 100 microM L-NAME. In summary, (-)epicatechin-induced endothelium-dependent relaxation is primarily mediated by nitric oxide and partially through nitric oxide-dependent activation of iberiotoxin-sensitive K+ channels. In addition, there may be a causal link between increased Ca2+ levels and nitric oxide release in response to (-)epicatechin.