巯亚硝基卡托普利对环匹阿尼酸引起的平滑肌细胞胞浆游离Ca^(2+)浓度升高作用的影响

Effects of S-nitrosocaptopril on cyclopiazonic acid-induced [Ca^(2+) ]_i change in rat aortic smooth muscle cells

目的 探讨巯亚硝基卡托普利 (S nitrosocaptopril,CapNO)对Ca2 + 池操纵性Ca2 + 内流信号转导过程的影响。方法 以Fura 2荧光探针测定胞浆游离Ca2 + 浓度([Ca2 + ]i)。结果 ①CapNO(2 0～ 12 0 μmol·L-1)呈浓度依赖性抑制环匹阿尼酸 (cyclopiazonicacid ,CPA)引起的[Ca2 + ]i 升高 ,80 μmol·L-1CapNO为最大效应浓度。相同浓度的captopril对CPA升高 [Ca2 + ]i 无明显抑制作用。②在 80 μmol·L-1CapNO抑制CPA引起 [Ca2 + ]i 升高作用的基础上 (31%± 11% ) ;随后加入 1μmol·L-1硝苯地平不能降低 [Ca2 + ]i,再加入 2 0 μmol·L-1SK&F96 36 5 (最大效应浓度 )可进一步降低 [Ca2 + ]i(5 4%± 18% ) ,其中SK&F96 36 5净抑制率为 2 4%± 10 % ,与SK&F96 36 5单独作用抑制率(5 4%± 11% )比较差异有显著性。③不同顺序给予最大效应浓度CapNO (80 μmol·L-1)和tyrphostinAG490 (2 μmol·L-1)对CPA引起 [Ca2 + ]i 升高存在交叉抑制作用。结论 CapNO可通过阻断电压依赖性Ca2 + 通道和Ca2 + 池操纵性Ca2 + 通道抑制CPA引起的 [Ca2 + ]i 升高 ,CapNO对CPA引起 [Ca2 + ]i 升高的阻断作用存在酪氨酸激酶 (Janus2亚型 )

AIM To study the characteristics of Ca 2+ channel mediated store operated Ca 2+ influx on rat vascular smooth muscle. METHOD Fura 2 fluorescence technique was used to investigate the [Ca 2+ ] i change. RESULTS ① S nitrosocaptopril (CapNO,20～120 μmol·L -1 ) produced a concentration dependent inhibitory effect on cyclopiazonic acid(CPA) induced [Ca 2+ ] i change. The maximal inhibitory effect(37%±17%) of CapNO was reached at a concentration of 80 μmol·L -1 . The same concentration of Captopril had no effects. ② Inhibition rate of 80 μmol·L -1 CapNO (The concentration of maximal effect, CME) on CPA induced [Ca 2+ ] i change was 30%±10%, subsequent addition of 1 μmol·L -1 Nif (CME)did not further produced the decrease effect (54%±18%). subsequent addition of 20 μmol·L -1 SK&F96365 (CME) further produced the decrease effect. The inhibitory effects of 20 μmol·L -1 SK&F96365 were significantly different in the cases of CapNO and Nif pretreatment(24%±10%) and non treatment (54%±11%). ③ The inhibitory effects of 2 μmol·L -1 tyrphostinAG490(AG490,CME) were significantly different in the cases of CapNO (CME) pretreatment (24%±9%)and non treatment (42%±10%). 80 μmol·L -1 CapNO effect on CPA induced [Ca 2+ ] i changes in AG490 pretreatment condition(18%±7%) was different from that in non treatment case(37%±10%). CONCLUSION S nitrosocaptopril obviously inhibits the opening of SOCC and VDCC, which mediates store operated Ca 2+ influx. The inhibitory effects of CapNO is associated with both sensitive to and non sensitive to tyrosine kinase (Janus2).