Journal
HYPERTENSION RESEARCH
Volume 32, Issue 12, Pages 1091-1096Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/hr.2009.160
Keywords
angiotensin receptor blocker; brain; oxidative stress; sympathetic nervous system
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Funding
- Japan Society for the Promotion of Science [B193290231]
- Salt Science Research Foundation [0738]
- Bayer Scholarship for Cardiovascular Research
- Japan Cardiovascular Foundation
- Health and Labor Sciences Research
- Daiichi-Sankyo Co, Tokyo, Japan [RNH-6270]
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We previously showed that oxidative stress in the brain is involved in the neural mechanisms of hypertension. Therefore, olmesartan, an angiotensin type 1 receptor blocker, might affect oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). Here, we evaluated the effects of olmesartan treatment using an in vivo electron spin resonance (ESR)/spin probe technique. Two groups of SHRSP were treated with either olmesartan (10 mg kg(-1) day(-1)) or hydralazine (Hyd, 20 mg kg(-1) day(-1))/hydrochlorothiazide (HCT, 4.5 mg(-1) kg day(-1)) for 30 days (n=5 for each). Systolic blood pressure decreased similarly in both groups after treatment. Heart rate and urinary norepinephrine (NE) excretion increased in rats treated with Hyd/HCT, but not in those treated with olmesartan. The in vivo ESR signal decay rates of the blood-brain barrier-permeable spin probe methoxycarbonyl-PROXYL were significantly higher in SHRSP brains than in age-matched normotensive Wistar-Kyoto rat brains (P<0.01; n=6 for each). Olmesartan attenuated the ESR signal decay rates in SHRSP brains, but Hyd/HCT did not. Intracerebroventricular infusion of active form of olmesartan, RNH-6270, reduced blood pressure and NE excretion, and the ESR signal decay rate was reduced in SHRSP brains. These findings indicate that olmesartan has anti-oxidative property in the brain without stimulating reflex-mediated sympathetic activity in SHRSP. Hypertension Research (2009) 32, 1091-1096; doi: 10.1038/hr.2009.160; published online 18 September 2009
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