Amelioration of Hypertensive Heart Failure by Amlodipine May Occur via Antioxidative Effects

Hasegawa, Hiroshi; Takano, Hiroyuki; Kohro, Takahide; Ueda, Kazutaka; Niitsuma, Yuriko; Aburatani, Hiroyuki; Komuro, Issei

doi:10.1291/hypres.29.719

Cited by 15 publications

(16 citation statements)

References 47 publications

(48 reference statements)

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“…There is much basic and clinical data indicating that amlodipine, in addition to having haemodynamic properties, exerts noncalcium channel-related modulation in the vasculature, such as antioxidant activity 13. Since the antioxidant activity of amlodipine, particularly in the heart, has not yet been well examined, we aimed to investigate the role of amlodipine in the heart and blood of rabbits.…”

Section: Discussionmentioning

confidence: 99%

Amlodipine attenuates oxidative stress in the heart and blood of high-cholesterol diet rabbits

Salehi

Mohammadi

Mirzaei

et al. 2012

Cardiovascular Journal of Africa

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IntroductionOxidative stress is a key component of atherosclerosis. It has been suggested that amlodipine inhibits oxidative stress. In this study, we evaluated the effects of amlodipine on the total antioxidant capacity of heart tissue and blood in 36 control and cholesterol-fed male New Zealand white rabbits.MethodsThe rabbits were divided into four groups (n = 9). Group 1 rabbits were fed a regular diet, group 2 were fed a diet with 2% cholesterol, group 3 were fed a regular diet plus 5 mg/kg/day oral amlodipine, and group 4 were fed 2% cholesterol diet plus amlodipine 5 mg/kg/day. At the end of eight weeks, blood samples were drawn and at the same time heart tissue was isolated and frozen in liquid nitrogen. After homogenisation, the solution was centrifuged and the light supernatant was stored at –80˚C. This was used for determination of glutathione peroxidase (GPX), superoxide dismutase (SOD) and (MDA) levels.ResultsEight weeks of amlodipine treatment significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides in the group on the hypercholesterolaemic diet (p < 0.05). In the blood, the level of thiobarbituric acid-reactive substances increased in the rabbits on the 2% cholesterol diet (group 2) and 2% cholesterol-plusamlodipine diet (group 4) and decreased in the amlodipineonly group (group 3) (p < 0.05). Lipid peroxidation in the heart tissue was similar to that in the blood, except in the amlodipine-only group (group 3). In the blood, the activity of total SOD (tSOD) decreased in the group on the 2% cholesterol diet (group 2) (p < 0.05) and markedly increased in the amlodipine-only (group 3) and 2% cholesterol-plusamlodipine groups (group 4) (p < 0.05).ConclusionAmlodipine decreased oxidative stress in the heart and blood and improved the lipid profile in cholesterolfed rabbits. Therefore, it may be considered a useful tool for the reduction of oxidative stress and improvement of lipid profiles in diseases related to atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Amlodipine attenuates oxidative stress in the heart and blood of high-cholesterol diet rabbits

Salehi

Mohammadi

Mirzaei

et al. 2012

Cardiovascular Journal of Africa

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“…Likewise, oral tempol or eplerenone given for six weeks to rats infused with Ang II and fed a high salt diet prevented the diastolic dysfunction and cardiac oxidative stress in this model also (Wang et al, 2008a). Oral tempol given to DSS rats fed a high salt diet prevented the development of left ventricular dilation and cardiac failure (Hasegawa et al, 2006) and, when given to rats infused with aldosterone and fed a high salt diet, reduced the collagen accumulation in the kidney and the fibrosis in the heart and aorta substantially (Iglarz et al, 2004). Thus tempol can prevent the development of left ventricular hypertrophy, cardiac inflammation and fibrosis and diastolic dysfunction and cardiac failure in salt sensitive rodent models by actions that may entail interruption of mineralocorticosteroid receptor signaling pathways.…”

Section: Major Organ Effects Of Tempolmentioning

confidence: 99%

Effects of tempol and redox-cycling nitroxides in models of oxidative stress

Wilcox

2010

Pharmacology & Therapeutics

417

344

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Tempol is a redox cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia.

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“…4-Hydroxy-TEMPO has been shown to act as a membrane-permeable superoxide dismutase mimetic (Matsui et al, 2006;Hasegawa et al, 2006). Cotreatment with 4-hydroxy-TEMPO partly suppressed the brain nitroNE and nitroE to 33.9 ± 3.3 pmol/g tissue and 27.3 ± 3.9 pmol/g tissue (mean ± SEM, n = 4) (p < 0.05) vs findings in rats administered kainic acid.…”

Section: Resultsmentioning

confidence: 92%

Oxidative stress increases 6‐nitronorepinephrine and 6‐nitroepinephrine concentrations in rat brain

Tsunoda

Uchino

Imai

et al. 2008

Biomedical Chromatography

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6-Nitronorepinephrine (nitroNE) and 6-nitroepinephrine (nitroE) are reaction products of nitric oxide and norepinephrine and epinephrine, respectively. The authors have previously reported a method for determination of nitroNE and nitroE in rat brain using high-performance liquid chromatography-peroxyoxalate chemiluminescence reaction detection. In this study, the effect of oxidative stress on nitroNE and nitroE concentrations in rat brain was examined using this method. After kainic acid administration in rats for 2 days, the concentrations of both nitroNE and nitroE in rat brains were found to have increased by 400-600%, which was partly suppressed by the co-administration of a superoxide dismutase mimetic. This indicates that oxidative stress might increase nitroNE and nitroE concentrations in rat brains.

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Amelioration of Hypertensive Heart Failure by Amlodipine May Occur via Antioxidative Effects

Cited by 15 publications

References 47 publications

Amlodipine attenuates oxidative stress in the heart and blood of high-cholesterol diet rabbits

Amlodipine attenuates oxidative stress in the heart and blood of high-cholesterol diet rabbits

Effects of tempol and redox-cycling nitroxides in models of oxidative stress

Oxidative stress increases 6‐nitronorepinephrine and 6‐nitroepinephrine concentrations in rat brain

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