有氧运动抑制高血压大鼠肠系膜动脉CaCCs通道蛋白TMEM16A表达上调

Aerobic exercise suppresses the upregulation of Ca CCs channel protein TMEM16A expression in mesenteric artery of hypertensive rats

目的探究有氧运动对高血压大鼠肠系膜动脉血管钙激活氯离子通道(Ca CCs)蛋白TMEM16A的表达及血管张力的影响。方法正常血压大鼠(WKY)随机分为正常运动组(WKY-EX)和正常安静组(WKY-SED);自发性高血压大鼠(SHR)随机分为高血压运动组(SHR-EX)和高血压安静组(SHR-SED)。运动组进行12周跑台运动(20 m/min,60 min/d,5 d/w,12 w)。12周有氧运动后,取各组大鼠的肠系膜动脉(3级)进行形态学观察、离体微血管张力测定及蛋白免疫印迹分析TMEM16A蛋白。结果高血压安静组大鼠心率(HR)和收缩压(SBP)水平较正常安静组显著增加(P<0.05),而12周有氧运动可显著降低SHR大鼠的体质量(BW)、HR、SBP水平(P<0.05)。高血压安静组大鼠肠系膜动脉血管平滑肌层厚度较正常安静组明显增加,而12周有氧运动可下调SHR大鼠的肠系膜动脉血管平滑肌层厚度。高血压安静组大鼠肠系膜动脉对去甲肾上腺素(NE)诱导的张力反应较正常安静组显著增加(P<0.05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉对NE诱导的张力反应。高血压安静组大鼠肠系膜动脉对特异性Ca CCs蛋白阻断剂(T16Ainh-A01)的敏感性较正常安静组显著增加(P<0.05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉对此药物的敏感性(P<0.05)。高血压安静组大鼠肠系膜动脉中Ca CCs通道蛋白TMEM16A的表达水平较正常安静组显著增加(P<0.05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉中Ca CCs通道蛋白TMEM16A的表达水平(P<0.05)。结论有氧运动可有效下调SHR大鼠血压,下调Ca CCs通道蛋白TMEM16A表达,抑制高血压诱导的Ca CCs通道的病理性代偿,从而引起血管功能的改善。

Aim To investigate the aerobic exercise-induced expression and vascular tone regulation of calciumactivated chloride channel(CaC Cs)protein TMEM16 A in mesenteric arteries of hypertensive rats.Methods The normotensive rats(WKY)were randomly divided into exercise group(WKY-EX)and sedentary group(WKY-SED).The spontaneously hypertensive rats(SHR)were also randomly divided into aerobic exercise group(SHR-EX)and sedentary group(SHR-SED).After one week acclimation,rats in the exercise groups were subjected to treadmill training(20 m/min,60 min/d,5 d/w,12 w).After 12 weeks,mesenteric arteries(the 3 rd branches)were collected for morphological observation,in vitro vascular tension determination and protein immunoblot analysis of protein TMEM16 A.Results Compared with WKY-SED,the body weight,heart rate,and systolic blood pressure were significantly increased in hypertension(P<0.05).However,they significantly dropped in SHR-EX group compared with its sedentary group(SHRSED,P<0.05).The thickness of the middle longer of the mesenteric artery in hypertensive rats was markedly increased,but it effectively decreased in SHR-EX compared with SHR-SED.The norepinephrine(NE)induced a marked increase of vascular tension in mesenteric arteries in all four groups,which was significantly higher in SHR-SED than that in WKYSED(P<0.05).Selective CaC Cs channel blocker(T16 Ainh-A01)induced concentration-dependent vasorelaxation in mesenteric arteries precontracted with norepinephrine.However,these effects were greatly decreased in SHR-EX group(P<0.05).Western blotting data showed that the protein expression of TMEM16 A was significantly increased with hypertension,whereas aerobic exercise could effectively ameliorate the changes(P<0.05).Conclusion Hypertension is associated with an increase of CaC Cs channel protein TMEM16 A expression,which is a negative feedback to regulate vascular contractility,whereas aerobic exercise can significantly weaken this hypertension-associated pathological upregulation of CaC Cs channels to improve the vascular function.