Wang Shuang-xi, Xiong Xiao-ming, Song Tao, Liu Li-ying
Department of Pharmacology, Pharmaceutical College, Central South University, Changsha 410078, China.
Acta Pharmacol Sin. 2005 Mar;26(3):329-33. doi: 10.1111/j.1745-7254.2005.00042.x.
To explore the effects of cariporide, a selective sodium-hydrogen antiporter inhibitor, on endothelial dysfunction induced by high glucose.
Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were measured in rat isolated aorta.
A 6-h incubation of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1 micromol/L) with high glucose, cariporide prevented the inhibition of EDR caused by high glucose in concentration-dependent manners. Similarly, high glucose decreased SOD activity and contents of NO, and increased MDA concentration in aortic tissue. Cariporide (1 micromol/L) significantly resisted the decrease of NO content and SOD activity, and elevation of MDA concentration caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1 micromol/L) alone had no effect on EDR, endothelium-independent relaxation and biochemical parameters.
Cariporide significantly prevented endothelial dysfunction induced by high glucose. The mechanisms of endothelial dysfunction induced by high glucose may involve the activation of sodium-hydrogen antiporter and the generation of oxygen-free radicals, but it is not related to the change of osmolarity.
探讨选择性钠氢逆向转运体抑制剂卡立泊来德对高糖诱导的内皮功能障碍的影响。
在大鼠离体主动脉中检测乙酰胆碱（ACh）诱导的内皮依赖性舒张（EDR）、硝普钠（SNP）诱导的非内皮依赖性舒张以及包括丙二醛（MDA）、超氧化物歧化酶（SOD）和一氧化氮（NO）在内的生化参数。
用高糖（44 mmol/L）孵育主动脉环6小时导致EDR显著抑制，但对非内皮依赖性舒张无影响。在卡立泊来德（0.01、0.1和1 μmol/L）与高糖共同存在的情况下孵育主动脉环6小时后，卡立泊来德以浓度依赖性方式阻止了高糖引起的EDR抑制。同样，高糖降低了主动脉组织中SOD活性和NO含量，并增加了MDA浓度。卡立泊来德（1 μmol/L）显著抵抗了高糖引起的主动脉组织中NO含量降低、SOD活性降低以及MDA浓度升高。单独使用甘露醇（44 mmol/L）或卡立泊来德（1 μmol/L）对EDR、非内皮依赖性舒张和生化参数无影响。
卡立泊来德显著预防了高糖诱导的内皮功能障碍。高糖诱导内皮功能障碍的机制可能涉及钠氢逆向转运体的激活和氧自由基的产生，但与渗透压的变化无关。
