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.