Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats

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The vascular protective effects of placebo, candesartan (1 mg kg(-1) per day) monotherapy, candesartan (1 mg kg(-1) per day) and amlodipine (1 mg kg(-1) per day) combination therapy, and candesartan (1 mg kg(-1) per day) and hydrochlorothiazide (HCTZ) (10 mg 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.