Antioxidant Enzyme Activities and Total Nitrite/ Nitrate Levels in the Collar Model. Effect of Nicardipine

Sözmen, Eser Yıldırım; Kerry, Zeliha; Uysal, Fevziye; Yetik, Günay; Yasa, Mukadder; Üstünes, Levent; Onat, Taner

doi:10.1515/cclm.2000.004

Cited by 21 publications

(9 citation statements)

References 28 publications

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“…In contrast, DETCA markedly increased superoxide production in collared arteries, suggesting that Cu 2ϩ /Zn 2ϩ -containing isoform(s) of SOD may play an important protective role in atherosclerotic arteries. This is despite the fact that total SOD activity in rabbit carotid arteries was reduced by 50% after 14 days with periarterial collars 25 and activity of extracellular SOD (the most abundant Cu 2ϩ /Zn 2ϩ -containing isoform of SOD in vascular tissue) is known to be suppressed in arteries from patients with coronary artery disease. 26 In the presence of SOD (albeit reduced activity) in atherosclerotic arteries, elevated superoxide may lead to increased generation of hydrogen peroxide.…”

Section: Discussionmentioning

confidence: 91%

Increased NADPH Oxidase Activity, gp91phox Expression, and Endothelium-Dependent Vasorelaxation During Neointima Formation in Rabbits

Paravicini

Gulluyan

Dusting

et al. 2002

Circulation Research

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Abstract-Reactive oxygen species including superoxide and hydrogen peroxide are important mediators in atherogenesis.We investigated the enzymatic source of vascular superoxide and its role in endothelium-dependent vasorelaxation during neointima formation. Silastic collars positioned around carotid arteries of rabbits for 14 days induced neointimal thickening. Using lucigenin-enhanced chemiluminescence, superoxide production was detectable in collared artery sections, but not in controls, only after inactivation of endogenous Cu 2ϩ /Zn 2ϩ -superoxide dismutase (Cu 2ϩ /Zn 2ϩ -SOD) with diethyldithiocarbamate (DETCA). Dihydroethidium staining indicated that endothelium and adventitia were the major sites of superoxide generation. Superoxide production in DETCA-treated collared arteries was enhanced further by NADPH and was inhibited by diphenyleneiodonium, suggesting NADPH oxidase was the source of the radical in collared arteries. Moreover, real-time PCR demonstrated 11-fold higher expression of the gp91phox subunit of NADPH oxidase in collared arteries than in controls. In vascular reactivity studies, endothelium-dependent vasorelaxation to acetylcholine did not differ between collared and control sections. However, treatment with DETCA reduced relaxations to acetylcholine in collared rings, but not in controls. NADPH further reduced relaxations to acetylcholine in DETCA-treated collared sections, but not in controls. In DETCA/NADPH-treated collared rings, sensitivity to nitroprusside, in contrast to acetylcholine, exceeded that of controls. Moreover, further treatment of such rings with exogenous Cu 2ϩ /Zn 2ϩ -SOD restored acetylcholine relaxations without altering nitroprusside responses. Thus, early neointimal lesions induced by periarterial collars are associated with elevated gp91phox expression and increased NAPDH-oxidase-dependent superoxide production in endothelium and adventitia. However, endothelium-dependent vasorelaxation is largely preserved due to the actions of Cu 2ϩ /Zn 2ϩ -SOD and increased smooth muscle sensitivity to nitric oxide. Not only is superoxide production increased in atherosclerotic arteries from humans, 1 rabbits, 2 and mice, 3 but ROS have also been shown to induce many proatherogenic cellular responses in vitro. These include inactivating endothelium-derived nitric oxide, 4 inducing endothelial cell apoptosis, 5 upregulating endothelial cell adhesion molecule expression, 6 stimulating the proliferation and migration of vascular smooth muscle cells, 7 and oxidatively modifying lipoproteins. 8 To our knowledge, only one study has attempted to characterize the oxidase responsible for superoxide production in atherosclerotic lesions. Warnholtz et al 9 demonstrated that superoxide production in aortas from Watanabe heritable hyperlipidemic and cholesterol-fed rabbits was markedly higher than that in controls. The enzyme responsible for superoxide production in these atherosclerotic arteries was membrane-associated, stimulated by NADH and NADPH, and inhibited by the flavoprotein inhib...

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Section: Discussionmentioning

confidence: 91%

Increased NADPH Oxidase Activity, gp91phox Expression, and Endothelium-Dependent Vasorelaxation During Neointima Formation in Rabbits

Paravicini

Gulluyan

Dusting

et al. 2002

Circulation Research

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“…Many gene encoding proteins responsible for vascular relaxation and free radical scavenging have been studied to prevent restenosis such as vascular endothelium growth factor (VEGF) (7 -9), superoxide dismutase (SOD), catalase (10), cyclooxygenase (COX) (11), and extracellular nitric oxide synthase (ecNOS) (12). A remarkable 20-fold increase in superoxide anion production occurs immediately after balloon injury and continues for up to 10 min when compared to uninjured arteries (13).…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Inhibitory Mechanisms of Magnolol on Rat Smooth Muscle Cell Proliferation

Chen

et al. 2005

J Pharmacol Sci

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Abstract. The pathological mechanism of percutaneous transluminal coronary angioplastyinduced restenosis has been attributed to outgrowth of vascular smooth muscle cells. Pretreatment with antioxidants has been shown to reduce restenosis. Magnolol, an active compound of Magnolia officinalis, has exhibited approximately 1,000 times more potent antioxidant effects than alpha-tocopherol. In this study, we demonstrate, using cytometric analysis, an approximate 61% reduction of smooth muscle cells progressing to the S-phase by 0.05 mg / ml of magnolol. A BrdU incorporation assay also showed a significant reduction (73%) of DNA synthesis using 0.05 mg / ml of magnolol. The protein level of the proliferating cell nuclear antigen was suppressed by approximately 48% using 0.05 mg / ml of magnolol. This was in agreement with the promoter activity of nuclear factor-kappa B, which was also attenuated by 0.05 mg / ml of magnolol. Since receptor interacting protein and caspase-3 protein expression levels were both increased by magnolol in a dose-dependent manner, the apoptotic pathway may mediate the inhibition of cell growth. Our finding that malondialdehyde formation was significantly inhibited by 0.05 mg / ml of magnolol further supported the antioxidant effect of magnolol. These studies suggest that magnolol might be a potential pharmacological reagent in preventing balloon injuryinduced restenosis.

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“…Both KCl- and 5-HT- induced maximal contractions were attenuated in collared rabbit carotid arteries (Beesley J, 1992, De Meyer et al , 1994, Sozmen et al , 2000, Ustunes et al , 1996, Van Put et al , 1995, Yasa et al , 1999). Consistent with other studies (De Meyer et al , 1992) collar placement induced a slight decrease in the sensitivity to ACh, but it did not reach to a statistically significant level.…”

Section: Discussionmentioning

confidence: 99%

Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

Yetik‐Anacak

Üstünes

Dilsiz

et al. 2010

Vascular Pharmacology

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Summary The anti-atherosclerotic effect of lacidipine has been attributed to its actions on cholesterol levels, lipid metabolism or oxidant stress in advanced disease. The purpose of the present experiments was to examine whether lacidipine is protective of intimal thickening and vascular dysfunction in early atherosclerosis in the absence of the hypertension and hypercholesterolemia. A second goal was to determine whether and to what extent MMP-9 and oxidant stress are involved in possible beneficial effects of lacidipine. Lacidipine treatment (5 mg/kg/day, p.o. for 3 weeks) significantly prevented the collar-induced intimal thickening. MMP-9 expressions were increased by collar but not effected by lacidipine treatment. Nitrotyrosine staining, a marker for oxidant stress was not changed neither by collar nor lacidipine treatment in early atherosclerosis. The enhanced sensitivity to serotonine and diminished sensitivity to acetylcholine in collared arteries were restored to normal levels with treatment. These results demonstrate that the lacidipine treatment prevents the collar-induced intimal thickening and accompanying vascular dysfunction in early atherosclerosis without cholesterol loading. These beneficial effects of lacidipine were not associated with changes in either MMP-9 expression or oxidant stress. However, enhanced endothelium dependent relaxations by lacidipine, suggest that vascular protective effects of nitric oxide may be at least partly, responsible from antiatherosclerotic effects of lacidipine

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Antioxidant Enzyme Activities and Total Nitrite/ Nitrate Levels in the Collar Model. Effect of Nicardipine

Cited by 21 publications

References 28 publications

Increased NADPH Oxidase Activity, gp91phox Expression, and Endothelium-Dependent Vasorelaxation During Neointima Formation in Rabbits

Increased NADPH Oxidase Activity, gp91phox Expression, and Endothelium-Dependent Vasorelaxation During Neointima Formation in Rabbits

Elucidating the Inhibitory Mechanisms of Magnolol on Rat Smooth Muscle Cell Proliferation

Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

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