氯沙坦联合螺内酯对老年自发性高血压大鼠基底动脉及认知功能的影响  

Effects of losartan combined with spironolactone on basilar artery and cognitive functions of elderly spontaneously hypertensive rats

作　　者：李晟 刘宇[2] 宋奇颖 李丽[1] 赵晓芳[1] 李晗 王蕾[1] LI Sheng;LIU Yu;SONG Qi-ying;LI Li;ZHAO Xiao-fang;LI Han;WANG Lei(Department of General Medicine,Shanxi Bethune Hospital Affiliated to Shanxi Medical University,Taiyuan 030032,Shanxi,China;Department of Pharmacology,Shanxi Medical University,Taiyuan 030001,Shanxi,China)

机构地区：[1]山西医科大学附属白求恩医院综合医疗科,太原030032 [2]山西医科大学药理学教研室,太原030001

出　　处：《第二军医大学学报》2020年第12期1414-1419,共6页Academic Journal of Second Military Medical University

基　　金：山西省回国留学人员科研资助项目(2017-124);山西省重点研发计划项目(201803D31145)。

摘　　要：目的研究血管紧张素受体阻断剂(ARB)氯沙坦与醛固酮受体拮抗剂螺内酯联合应用对老年自发性高血压大鼠(SHR)基底动脉功能及认知功能的影响。方法将18只老年雄性SHR随机分为SHR对照组、SHR氯沙坦组和SHR氯沙坦联合螺内酯组,每组6只,以6只相应周龄的雄性Wistar-Kyoto(WKY)大鼠作为阴性对照。适应性饲养4周后灌胃给药,SHR氯沙坦组给予氯沙坦20 mg/(kg·d),SHR氯沙坦联合螺内酯组给予氯沙坦20 mg/(kg·d)+螺内酯10 mg/(kg·d),药物干预4周。使用无创尾套法定期测量并记录各组大鼠血压,用Y-迷宫实验评价各组大鼠的空间记忆能力,用离体血管环技术检测大鼠基底动脉的收缩功能。结果SHR对照组收缩压较WKY大鼠对照组升高,SHR氯沙坦组和SHR氯沙坦联合螺内酯组收缩压较SHR对照组降低,且SHR氯沙坦联合螺内酯组降低幅度更大,差异均有统计学意义(P均<0.05)。Y-迷宫实验中,SHR对照组大鼠自发交替反应率与WKY大鼠对照组相比差异无统计学意义(P>0.05),SHR氯沙坦组的自发交替反应率较SHR对照组降低(P<0.05),SHR氯沙坦联合螺内酯组自发交替反应率较SHR氯沙坦组和WKY大鼠对照组降低(P均<0.05)。SHR对照组大鼠基底动脉在低浓度KCl溶液中收缩反应较WKY大鼠对照组更强,而在高浓度KCl溶液中收缩反应减弱;单独使用氯沙坦干预能够增强大鼠基底动脉收缩反应,而联合使用氯沙坦与螺内酯可使血管收缩反应明显减弱。结论ARB类药物联合醛固酮受体拮抗剂可有效控制血压,但血压控制过低对老年自发性高血压大鼠的认知功能可能产生不利影响。Objective To investigate the effects of losartan(an angiotensin receptor blocker[ARB])combined with spironolactone(an aldosterone receptor antagonist)on basilar artery and cognitive functions of elderly spontaneous hypertension rats(SHR).Methods Eighteen elderly male SHR rats were evenly randomized into SHR group(SHR control group),L group(losartan 20 mg/[kg·d]),and L+S group(losartan 20 mg/[kg·d]and spironolactone 10 mg/[kg·d]at the same time);six age-matched male Wistar Kyoto(WKY)rats with normal blood pressure served as controls(WKY group).Drug intervention lasted for 4 weeks by gavage after 4 weeks of adaptation.The blood pressure of rats in each group was measured by noninvasive tail-cuff method.Spatial memory ability was tested by Y-maze,and systolic and diastolic functions of rat basilar artery were tested with isolated vascular rings.Results The systolic blood pressure(SBP)of rats in SHR group was significantly higher than that in WKY group,while the SBP of rats in L group and L+S group was significantly lower than that in SHR group,with more significant decline in L+S group(all P<0.05).In the Y-maze test,no significant difference was found in spontaneous alternation rates between SHR group and WKY group(P>0.05).The spontaneous alternation rate of L group was significantly lower than that of SHR group(P<0.05).The spontaneous alternation rate of L+S group was significantly lower than those of L group and WKY group(both P<0.05).The systolic response of rat basilar artery in SHR group was stronger than that in WKYgroup in a low-concentration KCl solution,while it was weakened in a high-concentration KCl solution;losartan alone could enhance the systolic response of basilar artery,but the combined use of losartan and spironolactone could significantly reduce the systolic response.Conclusion ARBs combined with aldosterone receptor antagonists can effectively control blood pressure,but adverse effects may appear on the cognitive function of elderly SHR if the blood pressure becomes too low.

关 键 词：老年人 高血压 氯沙坦 螺内酯 认知功能 基底动脉 

分 类 号：R544.1[医药卫生—心血管疾病]