Sarpogrelate protects against high glucose-induced endothelial dysfunction and oxidative stress.

This study was designed to investigate the effect of sarpogrelate hydrochloride on impaired endothelium-dependent relaxation (EDR) induced by high glucose in isolated rat aorta. Both acetylcholine-induced EDR and sodium nitroprusside-induced endothelium-independent relaxation (EIR) were measured after the rings were exposed to high glucose in the absence and presence of sarpogrelate hydrochloride. Co-incubation of aortic rings with high glucose for 24h resulted in a significant inhibition of EDR, but had no effects on EIR. After incubation of the rings in the co-presence of sarpogrelate hydrochloride with high glucose for 24h, sarpogrelate hydrochloride significantly attenuated impaired EDR. This protective effect of sarpogrelate hydrochloride was abolished by N(G)-nitro-L-arginine methyl ester. Sarpogrelate hydrochloride significantly decreased superoxide anion (O(2)(-)) production and increased superoxide dismutase (SOD) activity and the nitric oxide (NO) release. These results suggest that sarpogrelate hydrochloride can restore impaired EDR induced by high glucose in isolated rat aorta, which may be related to scavenging oxygen free radicals and enhancing NO production.