Unknown

Cilostamide has been suggested to augment endothelium-derived hyperpolarizing factor (EDHF)-type relaxation by increasing the concentration of cAMP. It was investigated the effect of cilostamide on endothelium-derived hyperpolarization (EDH) per se in mesenteric arteries of Wistar rats using a conventional microelectrode technique. The resting membrane potential of the mesenteric arteries was significantly more negative in the presence of 10(-6) mol/L cilostamide compared with control conditions. Furthermore, EDH in response to 10(-6) mol/L acetylcholine (ACh) in the presence of 10(-5) mol/L indomethacin and 10(-4) mol/L N(G)-nitro-L-arginine was decreased in the presence of 10(-6) mol/L cilostamide by approximately 5 and 3.5 mV in proximal and distal arteries, respectively. Furthermore, in the presence of glibenclamide, ACh-induced EDH was unaffected by cilostamide, suggesting that the inhibition of ACh-induced hyperpolarization by cilostamide in the absence of glibenclamide may be due to the smaller driving force for hyperpolarization because of the more negative membrane potential under such conditions. It was suggested that cilostamide produced hyperpolarization by activating K(ATP) channels, presumably by increasing cAMP. However, cilostamide alone may not directly affect EDH.