自发性高血压大鼠淋巴细胞4-氨基吡啶敏感Kv通道电流变化及替米沙坦对其阻滞作用

Effects of telmisartan on 4-Aminopyridine-sensitive voltage dependant potassium channel of lymphocyte derived from spontaneously hypertensive rat

目的 研究不同周龄自发性高血压大鼠（SHR）外周血淋巴细胞4-氨基吡啶敏感Kv通道电流变化及替米沙坦对该通道的阻断作用,探讨淋巴细胞Kv在高血压病中的变化及替米沙坦对SHR淋巴细胞Kv通道的阻断作用.方法 取4周龄和16周龄SHR,雄性,使用密度离心法分离SHR外周血淋巴细胞,采用实时荧光定量PCR方法检测SHR外周血淋巴细胞Kv1.3 mRNA表达水平;全细胞膜片钳技术记录表达在淋巴细胞上Kv的电流密度,使用不同浓度替米沙坦灌流,观察其对SHR淋巴细胞Kv电流的影响.结果 （1）16周龄SHR淋巴细胞Kv电流密度为（119.0±9.6）pA/pF（n=30）,4周龄SHR为（59.0±7.2）pA/pF（n=30）,差异有统计学意义（P＜0.05）;（2）16周龄SHR收缩压和淋巴细胞Kv电流密度呈正相关（r=0.837,P＜0.05）;（3）16周龄SHR Kv1.3mRNA表达高于4周龄SHR（P＜0.05）;（4）替米沙坦浓度依赖性地阻滞SHR淋巴细胞Kv电流,不同浓度替米沙坦（10、30、100μmol/L）对Kv的阻断率分别为（10.5±3.4）%（n=30）、（45.8±3.7）%（n=30）、（81.6±4.2）%（n=30）,P＜0.01.结论 成年SHR淋巴细胞上存在更多有功能的Kv通道;替米沙坦对其有阻滞作用,其意义有待进一步研究.

Objective To study the effects of telmisartan on voltage dependant potassium channel （Kv）expression in lymphocytes from spontaneously hypertensive rat（SHR）. Methods Peripheral blood was collected from male SHR aged 16 and 4 weeks. Peripheral lymphocytes were separated from heparinized whole blood by standard Ficoll-Hypaque density gradient centrifugation. The whole-cell Kv currents were recorded with patch-clamp technique in the absence and presence of telmisartan（10,30,100 μmol/L）.Real-time PCR was used to determine Kv1.3 mRNA expression in lymphocytes. Results（1）The currents density of Kv was higher in lymphocytes from 16 weeks-old SHR[（119.0 ±9.6）pA/pF]than from 4 weeks-old SHR[（59.0±7.2）pA/pF, P〈0.05].（2）Currents density was positively correlated with systolic blood pressure in 16 weeks-old SHR（r= 0.837,P〈0.05）.（3）The lymphocytes Ky 1.3 mRNA expression was significantly higher in 16-weeks-old SHR than in 4-weeks-old SHR（P 〈 0. 05）.（4）Telmisartan reduced the whole-cell Ky currents in a concentration-dependent manner（10.5 ± 3.4）% at 10μmol/L,（45.8 ±3.7）% at 30 μmol/L and（81.6 ±4.2）% at 100 μmol/L, P〈0.01. Conclusions The lymphocyte Kv channel is upregulated in 16 weeks-old SHR suggesting a role of Kv in the pathophysiology of hypertension. Ky current in lymphocyte could be significantly blocked by telmisartan in a concentration dependent manner.