枸橼酸坦度螺酮对自发性高血压大鼠血压的影响及机制研究

摘要

目的:研究枸橼酸坦度螺酮(TC)对自发性高血压大鼠(SHR)血压的影响及机制.方法:将SHR随机分为模型组、阳性对照组(苯磺酸左旋氨氯地平片,2.5 mg/kg)和TC高、中、低剂量组(TC胶囊,40、20、10 mg/kg),每组8只,另设8只正常大鼠为正常对照组,每天ig药物1次,连续28 d.测量各组大鼠首次给药前及给药后0.5、1、1.5、2、3、4 h的收缩压(SBP),另每给药7 d测量1次1 h的SBP;末次给药后检测血清中一氧化氮(NO)含量,血浆中内皮素、肾素、血管紧张素Ⅱ(AngⅡ)和去甲肾上腺素(NE)含量.结果:单次给药时,与模型组比较,阳性对照组和TC各剂量组SHR首次给药后0.5、1 h时的SBP均明显降低(P<0.05或P<0.01),之后仅阳性对照组和TC高剂量组的SBP明显降低(P<0.05或P<0.01);多次给药时,与模型组比较,阳性对照组和TC高、中剂量组SHR给药第7、14、28天的SBP均明显降低(P<0.05或P<0.01).与模型组比较,阳性对照组和TC高剂量组SHR血清中NO含量明显升高,血浆中内皮素、肾素、AngⅡ和NE含量均明显降低(P<0.05或P<0.01);与阳性对照组比较,TC各剂量组SHR血清中NO含量明显降低,TC中剂量组SHR血浆中内皮素含量明显升高(P<0.05).结论:TC可明显降低SHR血压,其机制可能与调节NO和内皮素释放平衡,降低肾素、AngⅡ及NE含量有关.%OBJECTIVE:To study the effect and mechanism of tandospirone citrate (TC) on blood pressure in spontaneously hypertensive rats (SHR). METHODS:SHR were divided into model group,positive control group (Levamlodipine besylate tab-lets,2.5 mg/kg),TC high-dose,medium-dose,low-dose groups(TC capsules,40,20,10 mg/kg),8 in each group. Other 8 nor-mal rats were chosen as normal control group. The rats were intragastrically administrated medicines,once a day,for 28 d. Systolic blood pressure(SBP)before first administration and after 0.5,1,1.5,2,3,4 h of administration in each group were measured, and SBP after 1 h of administration were measured once every 7 d. After last administration,nitric oxide(NO)content in serum, endothelin,renin,angiotensin Ⅱ(Ang Ⅱ) and norepinephrine (NE) contents in plasma were detected. RESULTS:In single ad-ministration,compared with model group,SBP in 0.5,1 h in positive control group and TC groups after first administration were obviously decreased (P<0.05 or P<0.01),then SBP were obviously decreased only in positive control group and TC high-dose group (P<0.05 or P<0.01). In multiple administration,compared with model group,SBP in 7th,14th,28th day of administra-tion in positive control group and TC high-dose,medium-dose groups were obviously decreased(P<0.05 or P<0.01). Compared with model group,NO content in serum in positive control group,TC high-dose group were obviously increased;endothelin,re-nin,Ang Ⅱ and NE contents in plasma were obviously decreased (P<0.05 or P<0.01). Compared with positive control group, NO content in serum in TC groups was obviously decreased;endothelin,renin,Ang Ⅱ and NE contents in plasma were obviously increased in TC medium-dose group (P<0.05). CONCLUSIONS:TC can obviously decrease the blood pressure of SHR. The mechanism may be associated with adjusting the balance of NO and endothelin,and decreasing renin,AngⅡand NE contents.