Therapy with the Combination of Amlodipine and Irbesartan Has Persistent Preventative Effects on Stroke Onset Associated with BDNF Preservation on Cerebral Vessels in Hypertensive Rats

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• 作者：Yu Hasegawa ; Takashi Nakagawa ; Ken Uekawa ; Mingjie Ma…
• 关键词：Stroke ; SHRSP ; Combination therapy ; Amlodipine ; Irbesartan ; BDNF
• 刊名：Translational Stroke Research
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：7
• 期：1
• 页码：79-87
• 全文大小：508 KB
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• 作者单位：Yu Hasegawa (1)
  Takashi Nakagawa (1)
  Ken Uekawa (1)
  Mingjie Ma (1)
  Bowen Lin (1)
  Hiroaki Kusaka (1)
  Tetsuji Katayama (1)
  Daisuke Sueta (1)
  Kensuke Toyama (1)
  Nobutaka Koibuchi (1)
  Shokei Kim-Mitsuyama (1)
  
  1. Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto-shi, Kumamoto-ken, 8608556, Japan
  
• 刊物主题：Neurosciences; Neurology; Cardiology; Neurosurgery; Vascular Surgery;
• 出版者：Springer US
• ISSN：1868-601X

文摘

Although calcium channel blockers, angiotensin II receptor blockers, and combination therapy are effective for hypertensive patients, the significant differences among them against stroke onset are undetermined. In this study, we investigated the significant beneficial effects of the combination therapy using amlodipine and irbesartan against stroke onset in hypertensive rats. The animals were fed an 8 % sodium diet and assigned to (1) vehicle, (2) amlodipine (2 mg/kg/day), (3) irbesartan (20 mg/kg/day), and (4) amlodipine + irbesartan groups. The drugs were given orally until 35 days, and incidences of stroke-related signs and mortality and blood pressure (BP) were monitored. Cerebral blood flow (CBF), brain water content, weight of the brain and left ventricle, and histological evaluations were conducted for the treated groups at 42 days after the start of the high-salt diet. Amlodipine and the combination therapy significantly reduced BP compared with the vehicle. Although the rates of stroke-related signs and mortality were high in the vehicle group, the rats in the treatment groups were mostly healthy until 35 days. After all drugs were discontinued, stroke onset was frequently seen in the monotherapy groups until 42 days, but no signs were observed in the combination therapy group. Although there were no significant differences in CBF or brain edema, the combination therapy reduced blood–brain barrier disruption, white matter injury, and reactive astrocytes compared with irbesartan, and the combination also inhibited left ventricular hypertrophy and preserved brain-derived neurotrophic factor (BDNF) expression on cerebral vessels compared to the monotherapies. These data suggest that the combination therapy had a persistent preventive effect on stroke onset in hypertensive rats, and the effects might be associated with BDNF preservation on cerebral vessels. Keywords Stroke SHRSP Combination therapy Amlodipine Irbesartan BDNF