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

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）大鼠作为正常血压对照组。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舒缩功能。结果 SHR对照组收缩压较正常血压对照组WKY大鼠升高，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正常血压对照组WKY大鼠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氯沙坦组和正常血压对照组WKY大鼠降低（P均<0.05）。SHR对照组大鼠基底动脉在低浓度KCl溶液中收缩反应与正常血压对照组WKY大鼠相比更强，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。

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

Objective To study the effects of ARB losartan combined with aldosterone receptor antagonists antisterone on vertebrovascular function and cognition in the male elderly spontaneously hypertensive rats. Methods The male elderly spontaneously hypertensive rats were divided into 3 groups randomly, 6 in each group: SHR group, L group (losartan 20 mg/(kg?d)) and L+A group (losartan 20 mg/(kg?d) and antisterone 10 mg/(kg?d) at the same time). 6 WKY rats, age- and sex-matched, were taken as control group (WKY group). SHR group, L group, L+A group and WKY group were treated for 4 weeks by gavage after 4 weeks of adaptation. The blood pressure of each group was recorded. Y-maze was used to test the spatial learning memory ability of the rats. And the constriction and relaxation functions of the isolated arterial rings taken from the cerebrum were tested with the Multi Myogragh system. Results The SBP in SHR group was higher than that of WKY group significantly (P <0.05) . Compared with SHR group, the SBP of L group and L+A group were decreased significantly (P <0.05). The SBP in L+A group was decreased more significantly. Alternation behavior was taken as the index to evaluate the memory function of rats, no significant difference was found between the SHR group and WKY group (P >0.05). After drug intervention, the alternation behavior of SHR L group was significantly lower than that of SHR group (P <0.05) . The alternation behavior of SHR L+A group was significantly lower than that of SHR L group (P <0.05) , and at the same time was significantly lower than that in WKY group (P <0.05). Compared to WKYgroup, the basilar arteries of rats in SHR group had a stronger contractile response to low-concentration vasoconstrictor, and weaker in high-concentration. Losartan alone could enhance the basilar artery contractile response, while combined with antisterone could significantly weaken the vasoconstrictor response Conclusion ARBs combined with aldosterone receptor antagonists can effectively control blood pressure, but it has adverse effects on the cognitive function of elderly spontaneously hypertensive rats when the blood pressure was getting too low.