摘要
目的:探讨Exendin-4对大鼠离体血管内皮依赖性舒张反应和左心室乳头肌收缩力的影响其机制。方法:采用大鼠胸主动脉环检测Exendin-4对乙酰胆碱(ACh)诱导的内皮依赖性血管舒张功能影响的量效关系和时效关系;观察吲哚美辛、L-精氨酸、抗氧化剂、格列本脲和罗格列酮等药物对Exendin-4作用的影响;采用大鼠离体乳头肌检测Exendin-4对电刺激心肌收缩功能的影响。结果:Exendin-4呈浓度依赖性和时间依赖性地抑制ACh诱导的内皮依赖性血管舒张;环氧合酶抑制剂吲哚美辛和抗氧化剂PDTC对Ex-endin-4所致的血管内皮依赖性舒张功能损害均无明显影响;L-精氨酸、罗格列酮和格列本脲预处理血管环均能改善Exendin-4所致血管内皮功能损害;Exendin-4明显抑制乳头肌对电刺激的收缩反应,此抑制作用亦可被L-精氨酸预处理所逆转。结论:Exendin-4对大鼠离体血管内皮依赖性舒张和左心室乳头肌收缩具有抑制作用,可能与减少心血管细胞中NO生物活性有关。
Objective： To investigate the direct effect of exendin4 on endothelium-dependent relaxation of isolated rat aortas and contraction of rat left ventrictdar papillary muscles, and the possible mechanisms. Methods ： Aortic rings were exposed to exendin-4, and then the dose-responses and time-response relations of endothelium-de- pendent relaxant response to acetylcholine （ACh） were determined. The impacts of indomethacin, L-arginine, an- tioxidant, glibenclamide and rosiglitazone on the endothelium-dependent relaxant effects of exendin-4 were investi- gated in isolated rat aortas to explore the possible mechanisms. Isolated rat left ventricular papillary muscles were used to evaluate the effect of exendin4 on electrically stimulated myocardial contractility. Results： Exendin4 in- hibited the endothelium-dependent relaxant response to ACh in concentration-dependent and time-dependent man- ners, indicating that exendin-4 might be harmful for endothelial function. The impairment of endothelium-depend- ent relaxation induced by exendin-4 was not affected by pretreatment with the cyclooxygenase inhibitor indomethacin and the antioxidant PDTC, but was improved by pretreatment with the nitric oxide （N0） precursor L-arginine, and the NO synthesis or release enhancers rosiglitazone and glyburide. The contraction tension of papillary muscles elicited by electrical stimulation was significantly decreased by exendin-4, and this decrease was reversed by L-argi- nine. Conclusion： Exendin-4 can inhibit the endothelium-dependent relaxation of isolated rat thoracic aorta and contraction of isolated rat papillary muscles, and reduction of NO bioavailability in cardiovascular cells may be in- volved in the underlying mechanisms.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2013年第12期1438-1443,1461,共7页
Chinese Journal of New Drugs
基金
国家自然科学基金(81170778
30873062)
