Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats
Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats
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DOI：
10.1038/hr.2010.224
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发表时间：
2011-02-01
影响因子：
5.4
通讯作者：
Miyazaki, Mizuo
中科院分区：
文献类型：
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作者：
Takai, Shinji;Jin, Denan;Miyazaki, Mizuo
比较了安慰剂、坎地沙坦（每天1mg kg(-1)）单药治疗、坎地沙坦（每天1mg kg(-1)）和氨氯地平（每天1mg kg(-1)）联合治疗、坎地沙坦（每天1mg kg(-1)）和氢氯噻嗪（每天10mg kg(-1)）联合治疗2周对卒中易发、自发性高血压大鼠的血管保护作用。坎地沙坦单药治疗显著降低血压，两种联合治疗均显著低于单药治疗。各治疗组乙酰胆碱诱导的血管舒张明显强于安慰剂治疗组。此外，坎地沙坦加氨氯地平治疗组的弛豫明显强于坎地沙坦治疗组；然而，坎地沙坦和坎地沙坦加hctz治疗组之间没有显著差异。NADPH氧化酶亚基p22（phox）、gp91（phox）、NOX1、NOX4的血管基因表达在各治疗组均较安慰剂治疗组显著降低，且各组间差异无统计学意义。然而，在坎地沙坦加氨氯地平治疗组中观察到血管超氧化物歧化酶活性的显著增强，而在其他组中则没有。所有治疗组血管组织中丙二醛水平均显著降低。与坎地沙坦治疗组相比，坎地沙坦+氨氯地平治疗组有明显的衰减，但坎地沙坦+ hctz治疗组没有。免疫组织学分析显示，在所有治疗组中，4-羟基-2-壬烯醛阳性区域均显著减少，但坎地沙坦加氨氯地平治疗组的减少幅度明显大于坎地沙坦治疗组。因此，坎地沙坦和氨氯地平联合治疗可能通过减少氧化应激对血管组织具有强大的保护作用。高血压研究（2011）34,245-252；doi: 10.1038 / hr.2010.224;2010年11月25日在线发布
The vascular protective effects of placebo, candesartan (1 mg kg(-1) per day) monotherapy, candesartan (1 mg kg(-1) per day) and amlodipine (1mg kg(-1) per day) combination therapy, and candesartan (1mg kg(-1) per day) and hydrochlorothiazide (HCTZ) (10mg kg(-1) per day) combination therapy for 2 weeks were compared in stroke-prone, spontaneously hypertensive rats. Candesartan monotherapy significantly reduced blood pressure, and both combination therapies were equally and significantly lower than the monotherapy. Acetylcholine-induced vascular relaxation was significantly stronger in all therapeutic groups than in the placebo-treated group. Furthermore, the relaxation was significantly stronger in the candesartan plus amlodipine-treated group than in the candesartan-treated group; however, there was no significant difference between the candesartan-and candesartan plus HCTZ-treated groups. Vascular gene expressions of the NADPH oxidase subunits p22(phox), gp91(phox), NOX1 and NOX4 were significantly attenuated in all therapeutic groups compared with the placebo-treated group, and there were no significant differences among those groups. However, a significant augmentation of vascular superoxide dismutase activity was observed in the candesartan plus amlodipine-treated group, but not in other groups. Malondialdehyde levels in the vascular tissues were significantly attenuated in all therapeutic groups. Compared with the candesartan-treated group, significant attenuation was observed in the candesartan plus amlodipine-treated group, but not in the candesartan plus HCTZ-treated group. Immunohistological analysis showed that areas positive for 4-hydroxy-2-nonenal were significantly reduced in all therapeutic groups, but this reduction was significantly greater for the candesartan plus amlodipine-treated group than for the candesartan-treated group. Thus, candesartan and amlodipine combination therapy could have a powerful protective effect in vascular tissues via the reduction of oxidative stress. Hypertension Research (2011) 34, 245-252; doi: 10.1038/hr.2010.224; published online 25 November 2010