Contractile responses of diabetic rat aorta to phenylephrine at different stages of diabetic duration  

糖尿病大鼠病程的不同时期主动脉平滑肌对苯肾上腺素的收缩反应(英文)

作　　者：朱邦豪[1] 关永源[1] 闽军 贺华[1] 

机构地区：[1]中山医科大学药理教研室,广州中国510089

出　　处：《Acta Pharmacologica Sinica》2001年第5期65-69,共5页中国药理学报（英文版）

基　　金：Project supported by the Science Foundation of Guangdong Province (99M01304G);the National Natural Science Foundation of China (No 39970849)

摘　　要：AIM: To investigate the time-dependent changes in contractile responses of aorta to phenylephrine (Phe) in diabetic rats and age-matched control, and its possible mechanism. METHODS: At stages of 2-, 6-, and 12-week diabetic duration, aortic rings were studied for contractile responses to agonists in vitro. RESULTS: At the stage of 2-week diabetic duration, contractile responses to lower concentrations of phenylephrine were increased ( P < 0.05), but the maximal contraction of phenylephrine did not change. At the stage of 6-week diabetic duration, contractile responses to phenylephrine were increased (P < 0.01) at each concentration, and the maximal contraction was increased by approximately 40 %. However, at the stage of 12-week diabetic duration; 1) the maximal contractile response to Phe 10 μmol · L -1 was decreased (P <0.05), 2) in Ca2+ free edetic acid medium, Phe 10 μmol·L-1-induced transient contraction was also decreased (P < 0.05), 3) in Ca2+ free edetic acid medium, in the presence of nifedipine 10 μmol·L-1 and Phe 10 μmol·L-1, the Ca2+ repletion-caused contraction was not different from control, 4) in normal medium, cyclop-iazonic acid (CPA) 10 μmol·L-1-induced contraction was decreased ( P < 0.01). CONCLUSION: The results suggested that contractile responses to phenylephrine in diabetic rat aorta changed with the development of dia-betes , and the changes of functional Ca2 + store sizes and Ca2+ entry mainly through voltage-dependent Ca2+ channels were responsible for the alterations of contractile responses to phenylephrine in diabetes.目的:研究随着糖尿病的发生发展,大鼠主动脉平滑肌对苯肾上腺素等激动剂收缩反应的变化及其可能机制。方法:用链尿菌素诱导糖尿病后,在第2、6、12周,取主动脉环进行实验观察。结果:苯肾上腺素的浓度依赖性收缩反应曲线,与对照相比:在第2周,低浓度时(0.01-0.03μmol·L^(-1))明显增加(P<0.01),最大反应无明显变化;在第6周,各浓度点均显著增加,且最大收缩反应增加约40％;然而,在第12周1)苯肾上腺素10μmol·L^(-1)引起的最大收缩反应趋向降低(P<0.05),2)在无Ca^(2+)液,也较对照明显减小(P<0.05),3)在无Ca^(2+)液,在尼非地平1μmol· L^(-1)和苯肾上腺素10μmol·L^(-1)存 在下,复Ca^(2+)引起的收缩在两组间的差异未见显著性,4)在正常Krebs’液,环匹阿尼酸10μmol·L^(-1)引起的收缩反应较对照也显著减小(P<0.001)。结论:(1)在糖尿病的第2周,平滑肌α_1-肾上腺素能受体的敏感性增加。(2)糖尿病大鼠主动脉平滑肌对苯肾上腺素收缩反应的异常变化,与通过电压依赖性钙通道的Ca^(2+)内流大小、胞内功能性Ca^(2+)池大小及其胞内Ca^(2+)池耗竭后所引起的充电性内流变化密切相关。

关 键 词：experimental diabetes mellitus thoracic aorta PHENYLEPHRINE STREPTOZOCIN cyclopiazonic acid CALCIUM 

分 类 号：R587.1[医药卫生—内分泌]