链脲佐菌素诱发的大鼠糖尿病对cAMP介导的小冠状动脉舒张的影响

Effect of streptozotoxin-induced diabetes on cAMP-mediated dilation in rat small coronary arteries

目的:观察链脲佐菌素(streptozotoxin)诱发的大鼠糖尿病(STZ大鼠)对cAMP介导的小冠状动脉舒张的影响。方法:Wistar大鼠尾静脉注射streptozotoxin造模。应用视频显微测量技术(videomicroscopymeasurement)活体观察小冠状动脉的舒张。结果:(1)STZ诱发的大鼠糖尿病对经cAMP信号系统起作用的isoproterenol(ISO)引起的剂量依赖性舒张产生减弱,且与血管内皮无关。(2)STZ诱发的糖尿病大鼠的小冠状动脉对腺苷酸环化酶激活剂forskolin引起的舒张减弱,而腺苷酸环化酶抑制剂SQ22536可使舒张进一步减弱。(3)血管平滑肌细胞特异性电压依赖性钾通道阻断剂4-aminopyridine使STZ大鼠ISO和forskolin引起的舒张被阻断。(4)G蛋白刺激剂NaF使STZ大鼠小冠状动脉产生的舒张减弱,明显被抑制。结论:STZ诱发的大鼠糖尿病可以抑制cAMP信号系统介导的非内皮依赖性的小冠状动脉的舒张,此种作用是通过抑制平滑肌细胞电压依赖性钾通道的作用实现并受G蛋白影响。

AIM: To study the effect of streptozotoxin-induced diabetes on cAMP-mediated dilation of rat small coronary arteries (RSCA). METHODS: The diabetes models were induced by injection of streptozotoxin (STZ) to tail vein. The dilation of RSCA was examined by videomicroscopy measurement. RESULTS: (1) STZ diabetes reduced dilation induced by isoproterenol (ISO), operating through cAMP mechanism, in RSCA. This response was in a dose-dependent manner and endothelium-independent relation. (2) STZ diabetes reduced response of RSCA to adenylyl cyclase agonist forskolin and to adenylyl cyclase inhibitor SQ 22536. (3) The 4-aminopyridine, a Kv channel blocker of vascular smooth muscle, suppressed the dilation induced by ISO and forskolin in RSCA of STZ diabetes. (4) The NaF, a G-protein stimulator, reduced the response in RSCA of STZ diabetes. CONCLUSIONS: Although it is known that diabetes impairs endothelium-dependent vasodilation, the effect of diabetes on dilation mechanism independent of endothelium is not well understood. In the present study, it is demonstrated that dilation is reduced in STZ rat small coronary arteries via cAMP signal mechanism and Kv channel of vascular smooth muscle. The G-protein is able to influence this dilation mechanism.