title: Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Araki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Keiji
authors.initials: K
authors.lastname: Yasukawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009638:Norepinephrine / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000378:metabolism* / Q000517:prevention & control; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D006830:Hydralazine; C437965:olmesartan; D019255:NADPH Oxidases; D009638:Norepinephrine