KB-R7943 restores endothelium-dependent relaxation induced by advanced glycosylation end products in rat aorta

Abstract

ObjectivesThe aims of this study were to examine the effects of KB-R7943, an inhibitor of Na+/Ca2+ exchanger, on impaired endothelium-dependent relaxation (EDR) induced by advanced glycosylation end products (AGE) in isolated rat aorta. MethodsBoth acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured after the rings were exposed to AGE in the absence and presence of KB-R7943. ResultsCo-incubation of aortic rings with AGE (0.1g/L) 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 KB-R7943 (0.1–10μM) with AGE for 24h, KB-R7943 (10μM) significantly attenuated impaired EDR. Superoxide dismutase (200 U/mL) and l-arginine (3mM) could ameliorate the impairment of EDR caused by AGE, whereas d-arginine (3mM) had no effect on EDR. Similarly, AGE decreased superoxide dismutase (SOD) activity and the release of nitric oxide (NO), and increased superoxide anion (O2.−) production in aortic tissue. KB-R7943 (10μM) significantly decreased O2.− production and increased SOD activity and the NO release. ConclusionsThese results suggest that KB-R7943 attenuated the impairment of EDR elicited by AGE partially through scavenging oxygen free radicals.