Su Ying, Liu Xiao-Min, Sun Yan-Ming, Jin Hong-Bo, Luan Ying, Wu Yun
Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, Harbin, China.
Clin Exp Pharmacol Physiol. 2008 Oct;35(10):1265-70. doi: 10.1111/j.1440-1681.2008.05002.x. Epub 2008 Jul 9.
The present study was designed to investigate the effects of KB-R7943, an inhibitor of the Na+/Ca2+ exchanger, on impaired endothelium-dependent relaxation (EDR) induced by high glucose in rat isolated aorta. Both acetylcholine (ACh)-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR) were measured after aortic rings had been exposed to high glucose in the absence and presence of KB-R7943. Coincubation of aortic rings with high glucose (25 mmol/L) for 24 h resulted in a significant inhibition of EDR, but had no effect on EIR. After incubation of aortic rings in the presence of both KB-R7943 (0.1-10 micromol/L) and high glucose for 24 h, significantly attenuation of impaired EDR was observed. This protective effect of KB-R7943 (10 micromol/L) was abolished by superoxide dismutase (SOD; 200 U/mL) and l-arginine (3 mmol/L), whereas d-arginine (3 mmol/L) had no effect. Similarly, high glucose decreased SOD activity and the release of nitric oxide (NO) and increased superoxide anion (O2(-)) production in aortic tissue. KB-R7943 significantly decreased O2(-) production and increased SOD activity and NO release. These results suggest that KB-R7943 can restore impaired EDR induced by high glucose in rat isolated aorta, which may be related to the scavenging of oxygen free radicals and enhanced NO production.
本研究旨在探讨钠/钙交换体抑制剂KB-R7943对高糖诱导的大鼠离体主动脉内皮依赖性舒张功能受损（EDR）的影响。在主动脉环暴露于高糖且分别存在或不存在KB-R7943的情况下，测量乙酰胆碱（ACh）诱导的EDR和硝普钠（SNP）诱导的非内皮依赖性舒张功能（EIR）。主动脉环与高糖（25 mmol/L）共同孵育24小时导致EDR显著抑制，但对EIR无影响。在同时存在KB-R7943（0.1 - 10 μmol/L）和高糖的情况下将主动脉环孵育24小时后，观察到受损的EDR明显减轻。超氧化物歧化酶（SOD；200 U/mL）和L-精氨酸（3 mmol/L）可消除KB-R7943（10 μmol/L）的这种保护作用，而D-精氨酸（3 mmol/L）则无此作用。同样，高糖降低了主动脉组织中的SOD活性、一氧化氮（NO）释放并增加了超氧阴离子（O2(-)）的产生。KB-R7943显著降低了O2(-)的产生并增加了SOD活性和NO释放。这些结果表明，KB-R7943可以恢复高糖诱导的大鼠离体主动脉受损的EDR，这可能与清除氧自由基和增强NO产生有关。
