Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.
Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP.
Hirooka
Yoshitaka
Y
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. hyoshi@cardiol.med.kyushu-u.ac.jp
Kimura
Yoshikuni
Y
Nozoe
Masatsugu
M
Sagara
Yoji
Y
Ito
Koji
K
Sunagawa
Kenji
K
D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D002946:Cisterna Magna; D004578:Electron Spin Resonance Spectroscopy; D006339:Heart Rate / Q000187:drug effects; D007267:Injections; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D020521:Stroke / Q000235:genetics / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002121:Calcium Channel Blockers; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D017311:Amlodipine; D009638:Norepinephrine