阿托伐他汀对自发性高血压大鼠肠系膜动脉平滑肌细胞大电导钙激活钾通道的影响

目的: 探讨阿托伐他汀对自发性高血压大鼠(SHR) 动脉血压及肠系膜动脉平滑肌细胞大电导钙激活钾通道(large-conductance calcium-activatedpotassium channel, BKCa,MaxiK) 的影响。方法: 选取雄性9 周龄SHR12 只, 随机分为阿托伐他汀组(AVT 组) 、蒸馏水组(DW 组), 每组6 只, 以Wistar-Kyoto 大鼠为对照组(WKY 组) (n =6) 。AVT 组以AVT 加适量蒸馏水灌胃10 周(50 mg·kg^-1·d^-1) 。观察给药前后大鼠腹主动脉血压的变化, 测定大鼠血清TC 、TG 及高密度脂蛋白胆固醇(HDL-C) 含量。利用膜片钳全细胞模式记录肠系膜动脉平滑肌细胞钾电流、用四乙胺阻断大电导钙激活钾通道后的电流、膜电容, 以计算BKCa 电流值、电流密度。结果: AVT 组腹主动脉血压明显低于DW 组[(171±8) mm Hg vs (190±10) mm Hg, P<0.01] (1 mm Hg =0.133 kPa) ;与DW 组相比,AVT 组肠系膜动脉平滑肌细胞BKCa电容减低[(23.8 ±2.6) pF vs (30.0±2.5) pF, P<0.01] 而电流密度则显著高于DW 组[(13.2±1.2) pA /pF vs (9.2±1.2) pA /pF, P<0.01) ], 与WKY 组比较未见明显差异。结论: 长期应用阿托伐他汀可降低SHR 血压, 其机制可能是AVT 影响BKCa 活性, 调节血管张力。

Effects of atorvastatin on large-conductance calcium-activated potassium channel of arteria mesenterica minor smooth muscle cells in spontaneously hypertensive rats

AIM: To evaluate the effects of atorvastatin on large-conductance calcium-activated potassium channel(BKCa, MaxiK) of arteria mesenterica minor smooth muscle cells in spontaneously hypertensive rats. METHODS: Twelve male spontaneously hypertensive rats(SHR) aged 9 weeks were randomly divided into atorvastatin treatment group(ATV group, n =6) and distilled water group(DW group, n =6), and 6 Wistar-Kyoto rats were as normal control group (n = 6). Atorvastatin and appropriate distilled water were administered to rats in ATV group (50 mg·kg^-1·d^-1) for 10 weeks by intragastric administration. The changes of abdominal aortic blood pressure were observed and the contents of TC, TG, LDL-C in serum were measured before and after treatment. The arterial mesenterica smooth muscle cell potassium current were recorded using whole cell patch clamp. The BKCa membrane capacitance and its current densitys were detected after the BKCa was blocked using tetraethylammonium. RESULTS: The abdominal aorta blood pressure in ATV group was much lower than that in DW group[(171 ±8) mm Hg vs(190 ±10) mm Hg, P < 0.01] (1 mm Hg =0.133 kPa). The BKCa membrane capacitance of arteria mesenterica smoothmuscle cell in ATV group was decreased [(23.8 ±2.6) pF vs (30.0 ±2.5) pF, P <0.01] and the current density was significantly increased[(13.2 ±1.2) pA /pF vs (9.2 ±1.2) pA /pF, P <0.01) compared with that in DW group, but there was no difference compared with that in WKY group. CONCLUSION: Long-term administration of atorvastatin can effectively reduce the blood pressure of SHR. The mechanism probably is the BKCa is activiated by atorvastatin and the angiotasis is adjusted.