Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats
| Autor: | Takashi Shimosato, Denan Jin, Shinji Takai, Hiroshi Sakonjo, Mizuo Miyazaki |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Combination therapy Physiology Vasodilator Agents Tetrazoles Pharmacology medicine.disease_cause Placebo chemistry.chemical_compound Hydrochlorothiazide Malondialdehyde Rats Inbred SHR Internal Medicine Animals Medicine Amlodipine Rats Wistar Diuretics Antihypertensive Agents Superoxide Dismutase business.industry Biphenyl Compounds NADPH Oxidases Acetylcholine Rats Stroke Vasodilation Candesartan Blood pressure Gene Expression Regulation chemistry Blood Vessels Benzimidazoles Drug Therapy Combination Cardiology and Cardiovascular Medicine business Oxidative stress medicine.drug |
| Zdroj: | Hypertension Research. 34:245-252 |
| ISSN: | 1348-4214 0916-9636 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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