The Protective Effect of 17β-Estradiol on Vasomotor Responses of Aorta from Cholesterol-Fed Rabbit Is Reduced by Inhibitors of Superoxide Dismutase and Catalase

Ghanam, Khadija; Javellaud, James; Ea-Kim, Leng; Oudart, Nicole

doi:10.1006/bbrc.1998.9238

Cited by 27 publications

(19 citation statements)

References 21 publications

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“…18 Gender differences are a common finding in many such studies of maternal dietary imbalance, 22,41 although the mechanisms behind this remain to be elucidated. One candidate is estrogen and the estrogen receptors (ER␣ and ER␤), which are known to have a number of favorable cardiovascular actions, including increasing NO bioavailability and reducing oxidative stress, [42][43][44] all of which are proposed to underpin the increase of cardiovascular disease in postmenopausal women. 45 We have previously demonstrated impaired 17␤-estradiol-mediated vasodilatation in MAs of PR dams, 4 suggesting that alterations in estrogen may indeed have a role in this model.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

et al. 2009

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Abstract-Maternal protein restriction in rats leads to endothelial dysfunction and decreased NO bioavailability in the offspring. Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) are recognized to have pleiotropic actions including increasing NO bioavailability and reducing inflammation and oxidative damage. This study assessed statin treatment on vascular function in a model of endothelial dysfunction, which is independent of dyslipidemia. Wistar rats were fed a control (18% casein) or protein-restricted (9% casein) diet throughout pregnancy. At weaning, a subset of the protein-restricted group was given atorvastatin (10 mg/kg per day) in the drinking water. At 145 days of age, offspring were euthanized by CO 2 inhalation. Plasma samples were collected for markers of inflammation, vascular reactivity of the thoracic aorta, and small mesenteric arteries were assessed on the wire myograph, and tissues were snap frozen for molecular biology analysis. Thoracic aorta endothelial-dependent vasodilatation was attenuated in the male offspring from both protein-restricted groups compared with controls (PϽ0.05) but was similar in females (P value not significant). Endothelial-dependent dilatation of mesenteric arteries was attenuated in male and female protein-restricted offspring (PϽ0.05) and was corrected by atorvastatin. Maternal protein restriction increased plasma inflammatory markers granulocyte chemotactic protein, lipocalin-2, and ␤ 2 -microglobulin in male and C-reactive protein in female offspring (PϽ0.05). Atorvastatin had no effect on inflammatory markers in the males but restored C-reactive protein to control levels in the females (PϽ0.05). Aortic and mesenteric artery mRNA levels of endothelial NO synthase, superoxide dismutase 1, and tumor necrosis factor-␣ were unchanged. These data suggest that atorvastatin can restore endothelial function in this model, but its effects are gender specific and dependent on the vascular bed. Key Words: statins (atorvastatin) Ⅲ experimental models Ⅲ fetal programming Ⅲ vascular biology Ⅲ endothelium Ⅲ nitric oxide Ⅲ inflammation T here is considerable evidence that the etiology of cardiovascular and metabolic diseases has origins partly in the developmental environment. 1 A widely used animal model to study this phenomenon is the rat, in which the restriction of dietary protein during pregnancy leads to raised blood pressure and endothelial dysfunction in the offspring. [2][3][4] Increasingly, evidence from this model points to a disruption to the NO pathway as a key component of the underlying pathophysiology. 4,5 The healthy vascular endothelium plays an important role in maintaining vascular tone through the release of factors including NO, prostacyclin, and endothelial-derived hyperpolarizing factor. 6 The importance of a healthy endothelium is seen in cardiovascular and metabolic diseases, where endothelial dysfunction is associated with atherosclerosis, hypertension, and the metabolic syndrome. 7-9 Important in the development of such endothelial ...

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Section: Discussionmentioning

confidence: 99%

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

et al. 2009

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“…Because NO is readily inactivated by superoxide, the bioactivity of endotheliumderived NO (EDNO) is dependent on local activity of superoxide dismutase (SOD) [Lynch et al, 1997]. This statement is well supported by the study of Ghanam et al [1998], who found that diethyl dithiocarbamate, a specific inhibitor of Cu/Zn SOD, reduced relaxation response of rabbit aorta to acetylcholine down to the level obtained in cholesterol-fed rabbits, which suggests the possible participation of SOD in the response of NO. In support of this postulation, Lynch et al [1997] concluded from their study that chronic inhibition of Cu/Zn SOD inhibits EDNO arterial relaxation through two mechanisms: 1) direct inactivation of NO, and 2) lipid peroxidation that preferentially interrupts receptor-mediated stimulation of EDNO.…”

Section: Discussionmentioning

confidence: 88%

Regression of early events of atherosclerosis in hypercholesterolemic rabbits by prophylactic treatment with nitroderivative of acetyl salicylic acid

Khattab

Moustafa

Burgaud

2001

Drug Development Research

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The potential of a newly developed compound, nitro-aspirin (NO-aspirin, NCX-4016), on regression of early atherosclerotic events in hypercholesterolemic rabbit (HypR) was examined. Hypercholesterolemia was induced by feeding rabbits 2% cholesterol-enriched diet for 28 days. During this induction period, HypRs were divided into two groups: one was given an oral single daily dose of 56 mg/kg/day NOaspirin in olive oil, whereas the other received olive oil alone and served as a control. A normal group of rabbits fed plain chow diet plus olive oil was also included. At the end of the 28 days, samples from blood, aorta, heart, and coronary arteries were separated for biochemical and histopathological examination. Tissues from HypR aorta and coronaries developed major changes that include formation of large intimal plaques, endothelial gaps with marked accumulation of foam cells. Highly significant increases in serum triglycerides and malondialdehyde and a decrease in reduced glutathione (GSH) in heart and aorta were also observed. Administration of NO-aspirin markedly improved aortic and coronary architecture to almost normal appearance. NO-aspirin also improved the antioxidant status in aorta and heart by increasing GSH levels and ameliorating malondialdehyde accumulation. These data support prophylactic use of NO-aspirin in regression of atherosclerosis. Drug Dev. Res. 53:237-243, 2001.

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“…Recently in vitro experiments by Arnal et al [1] and Bolego et al [4] suggested that estrogen improves the content of bioactive NO release in endothelial cells and acetylcholine (ACh)-induced vasodilation, which may be due to decreased superoxide formation. The protective effect of 17ß-estradiol (E 2 ) on vasomotor responses in the aorta from cholesterol-fed rabbits is reduced by inhibitors of superoxide dimutase and catalase [8]. Thus, the present study is the first in vitro experiment to test this hypothesis.…”

Section: Introductionmentioning

confidence: 79%

Tetrahydrobiopterin Improves Vascular Endothelial Function in Ovariectomized Rats

Lam

Ho²,

Yen

2002

J Biomed Sci

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The goal of the present study is to investigate the role of tetrahydrobiopterin (BH₄) in the vascular response in ovariectomized rats. Rats were randomly assigned to two groups: (1) sham group: sham-operated female rats, and (2) Ovx group: rats were ovariectomized. Our results have shown that the plasma 17β-estradiol levels in the Ovx group at the end of the experiment were significantly lower than in the sham group. Vasoreactivity assessed with intact aortic rings indicated that the phenylephrine-induced vasocontractile response to aortic rings from the Ovx group was greater than that of the sham group. In contrast, the vasodilator responses to acetylcholine and L-arginine (L-Arg) in the sham group were significantly greater than in the Ovx group. Differences in vasoreactivity in denuded aorta between the two groups were not noted. Moreover, exogenous BH₄ significantly restored L-Arg-induced vasodilator responses in the Ovx group. However, this improvement effect was not found in the sham group. In addition, there were significant increases in superoxide anion production in aortic tissue and significant decreases in plasma nitric oxide levels in the Ovx group. Furthermore, BH₄ contents in the aorta in the Ovx group were significantly decreased compared with the sham group. In conclusion, the present study demonstrates that the impairment of vascular reactivity was found in the ovariectomized rats. The possible mechanism of this defect may have resulted from the deficiency of available BH₄. Thus, this study may provide a novel therapeutic strategy for the treatment of postmenopausal cardiovascular disorders.

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The Protective Effect of 17β-Estradiol on Vasomotor Responses of Aorta from Cholesterol-Fed Rabbit Is Reduced by Inhibitors of Superoxide Dismutase and Catalase

Cited by 27 publications

References 21 publications

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

Atorvastatin Restores Endothelial Function in Offspring of Protein-Restricted Rats in a Cholesterol-Independent Manner

Regression of early events of atherosclerosis in hypercholesterolemic rabbits by prophylactic treatment with nitroderivative of acetyl salicylic acid

Tetrahydrobiopterin Improves Vascular Endothelial Function in Ovariectomized Rats

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