缬沙坦干预对缺氧性肺动脉高压大鼠大电导钙激活钾通道的影响

目的：观察缬沙坦对缺氧性肺动脉高压（PAH）大鼠肺动脉平滑肌细胞大电导钙激活钾通道（large-conductance calcium-activated potassiumchannel,BKCa,MaxiK）的影响。方法：选取二级健康7周龄雄性SD大鼠30只,随机分为A组：对照组,B组：PAH模型组,C组：缬沙坦干预组。测定3组大鼠肺动脉平均压（PAMP）,利用膜片钳全细胞模式记录肠系膜动脉平滑肌细胞膜电容、钾电流以及用四乙胺阻断BKCa后的电流,以计算BKCa电流值及其电流密度值,免疫组织化学染色观察BKCa蛋白的表达。结果：B组PAMP明显高于A组（P〈0.01）,而膜电容、BKCa电流和电流密度及BKCa蛋白表达平均积分吸光度（iOD）值均明显低于A组（P〈0.05）。与B组相比较,给予缬沙坦干预后,C组的PAMP显著下降（P〈0.01）,BKCa电流和电流密度均有不同程度增加（P〈0.05）,而BKCa蛋白表达iOD值则无明显变化。结论：缬沙坦可有效降低缺氧性肺动脉高压大鼠的肺动脉压力,其机制可能是通过增加肺动脉平滑肌细胞BKCa的活性实现的。

Effects of valsartan on BKCa of hypoxic pulmonary hypertensive rats

AIM: To observe the effects of valsar-tan on the large-conductance calcium-activated potassi-um channel (BKCa)of smooth muscle cells isolated from hypoxia-pulmonary artery hypertension (PAH) rats. METHODS: Thirty second-grade healthy SD male rats aged 7 weeks were selected, and divided ran-domly into 3 groups: Group A was control group, Group B was PAH group and Group C was valsartan in-tervention group with 10 rats in each group. The mean pulmonary artery pressure (PAMP)was measured in 3 groups. The arteria mesenterica smooth muscle cell ca-pacitance of membrane (Cm), potassium current, and the current after BKCa was blocked by tetraethylammo-nium(TEA) were recorded by whole cell patch clamp and the BKCa current and the BKCa current density were calculated. The BKCa protein expression was measured by immuno-histochemical stain. RESULTS: Compared with Group B, the PAMP was lower than that in Group A or Group C (P < 0.01), the mem-brane capacitance, BKCa current , current density and iOD value in Group A were higher (P < 0.05), the BKCa current , BKCa current density were increased at different degrees in Ggroup C ( P < 0.05), but there was no change in iOD value. CONCLUSION:Valsar-tan can effectively reduce pulmonary pressure in hy-poxia- pulmonary artery hypertension rats. The mecha-nism was probably the BKCa was activiated by valsar-tan.