Amlodipine reduced oxidative stress in the brain and decreased urinary norepinephrine excretion in stroke-prone spontaneously hypertensive rats without inducing reflex sympathoexcitation.
Does amlodipine reduce oxidative stress in the brains of stroke-prone spontaneously hypertensive rats?
Amlodipine reduces brain oxidative stress and sympathetic nerve activity in stroke-prone spontaneously hypertensive rats, independent of its blood pressure-lowering effect.
Absolute Event Rate: 0.87% vs 1.68%
p-value: p=<0.05
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 et al. (2006) studied Hypertension (Stroke-Prone Spontaneously Hypertensive Rats). Amlodipine vs. Nicardipine (10 mg/kg/day), Hydralazine (20 mg/kg/day), or vehicle was evaluated on Urinary norepinephrine excretion (μg/day) after treatment (p=<0.05). Amlodipine reduced oxidative stress in the brain and decreased urinary norepinephrine excretion in stroke-prone spontaneously hypertensive rats without inducing reflex sympathoexcitation.