Role of lipid peroxidation and the glutathione‐dependent antioxidant system in the impairment of endothelium‐dependent relaxations with age

Rodríguez-Martínez, María; Alonso, María J.; Redondo, Juliana; Salaíces, Mercedes; Marı́n, Jesús

doi:10.1038/sj.bjp.0701595

Cited by 45 publications

(22 citation statements)

References 46 publications

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“…Animal studies have demonstrated that O 2 Ϫ generation increases with age in the rat aorta and contributes to the age-related decrease in vasodilatation (25). The incubation of tail artery segments with MDA has been found to reduce ACh-induced relaxation in both younger and older rats (43). In the present work, we have postulated that low-dose aspirin treatment could prevent such age-related oxidative damage to the vascular wall.…”

Section: Discussionmentioning

confidence: 76%

“…endothelium; intima/media; vasodilatation; oxidative stress AGE-ASSOCIATED CHANGES SUCH as endothelial dysfunction are involved in the significantly increased risk of cardiovascular complications and microthrombus formation in the elderly patient population (44). The presence of endothelial dysfunction in the coronary or peripheral circulation has been shown to constitute a risk factor for cardiovascular events independent of the development of atherosclerosis or other vascular risk factors (22,(43)(44)(45). There is emerging evidence that age-associated endothelial dysfunction is related to the local formation of reactive oxygen and nitrogen species within and in the vicinity of the vascular wall (13,25,36,43,49).…”

mentioning

confidence: 99%

“…The presence of endothelial dysfunction in the coronary or peripheral circulation has been shown to constitute a risk factor for cardiovascular events independent of the development of atherosclerosis or other vascular risk factors (22,(43)(44)(45). There is emerging evidence that age-associated endothelial dysfunction is related to the local formation of reactive oxygen and nitrogen species within and in the vicinity of the vascular wall (13,25,36,43,49). Therapeutic approaches capable of preventing or reversing age-related endothelial dysfunction may thus help to reduce cardiovascular risk in the elderly.…”

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confidence: 99%

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Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

Bulckaen¹,

Prévost²,

Boulanger³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Agerelated endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2Ј-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60-and 84-wk-old mice (P Ͻ 0.05); 68-wkold mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 Ϯ 4 vs. 66.3 Ϯ 5%; P Ͻ 0.05). Aspirin treatment decreased 8-OHdG levels (P Ͻ 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress. endothelium; intima/media; vasodilatation; oxidative stress AGE-ASSOCIATED CHANGES SUCH as endothelial dysfunction are involved in the significantly increased risk of cardiovascular complications and microthrombus formation in the elderly patient population (44). The presence of endothelial dysfunction in the coronary or peripheral circulation has been shown to constitute a risk factor for cardiovascular events independent of the development of atherosclerosis or other vascular risk factors (22,(43)(44)(45). There is emerging evidence that age-associated endothelial dysfunction is related to the local formation of reactive oxygen and nitrogen species within and in the vicinity of the vascular wall (13,25,36,43,49). Therapeutic approaches capable of preventing or reversing age-related endothelial dysfunction may thus help to reduce cardiovascular risk in the elderly.Age-related endothelial-dependent relaxation (EDR) decreases in the large vessels of different animal species including humans (36). EDR in response to acetylcholine (ACh) decreases with age in the rat aorta: the maximal relaxation effect of ACh is 100% in 4-to 6-wk-old, 50% in 3-to 6-mo-old, and 25% in 12-to 25-mo-old rats (29). The agerelated decrease in EDR varies from one vessel to another and from one species to anot...

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Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

Bulckaen¹,

Prévost²,

Boulanger³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…The mechanisms responsible for this age-related cardiovascular dysfunction have not yet been clearly established. This impairment is, at least in part, related to the increased local formation of reactive oxygen and nitrogen species in the myocardium and vasculature (Inoue and Inoue, 1996;Rodriguez-Martinez et al, 1998;van der Loo et al, 2000). Superoxide anion inter- …”

Section: Discussionmentioning

confidence: 99%

A New, Potent Poly(ADP-ribose) Polymerase Inhibitor Improves Cardiac and Vascular Dysfunction Associated with Advanced Aging

Pacher

Vaslin

Benkó

et al. 2004

J Pharmacol Exp Ther

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Increased production of reactive oxygen and nitrogen species has recently been implicated in the pathogenesis of cardiac and endothelial dysfunction associated with atherosclerosis, hypertension, and aging. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP), which in turn contributes to cardiac and vascular dysfunction in various pathophysiological conditions including diabetes, reperfusion injury, circulatory shock, and aging. Here, we investigated the effect of a new PARP inhibitor, INO-1001, on cardiac and endothelial dysfunction associated with advanced aging using Millar's new Aria pressure-volume conductance system and isolated aortic rings. Young adult (3 months old) and aging (24 months old) Fischer rats were treated for 2 months with vehicle, or the potent PARP inhibitor INO-1001. In the vehicle-treated aging animals, there was a marked reduction of both systolic and diastolic cardiac function and loss of endothelial relaxant responsiveness of aortic rings to acetylcholine. Treatment with INO-1001 improved cardiac performance in aging animals and also acetylcholine-induced, nitric oxide-mediated vascular relaxation. Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging.Poly(ADP-ribose) polymerase (PARP) is the most abundant nuclear enzyme of eukaryotic cells. When activated by DNA single-strand breaks, PARP initiates an energy-consuming cycle by transferring ADP ribose units from NAD ϩ to nuclear proteins. This process results in rapid depletion of the intracellular NAD ϩ and ATP pools, slowing the rate of glycolysis and mitochondrial respiration, eventually leading to cellular dysfunction and death (reviewed in Virá g and Szabó 2002). PARP can also regulate the expression of various inflammatory mediators such as inducible nitric-oxide synthase, tumor necrosis factor-␣, and intracellular adhesion molecule-1. Suppression of expression of inducible nitric-oxide synthase, tumor necrosis factor-␣, and intracellular adhesion molecule-1 has been reported in PARP-deficient mice and in the presence of pharmacological inhibitors of the enzyme (reviewed in Virá g and Szabó 2002).Overactivation of PARP represents an important mechanism of tissue damage in pathological conditions associated with oxidative/nitrosative stress, including myocardial reperfusion injury, stroke, circulatory shock, autoimmune ␤-cell destruction, diabetic complications, and various forms of heart failure (Szabó et al., 1997;Thiemermann et al., 1997;Zingarelli et al., 1998; Soriano et al., 2001a,b; Pacher et al., 2002a-f;Virá g and Szabó 2002;Szabó 2004a

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“…Rodriguez-Martinez et al (29) re ported that the MDA levels increased two and threefold in 24-and 30-mo-old rats when compared to 6-mo-old rats, and therefore concluded that lipid peroxidation in creases with age. From our data, both the 50% and 95% ethanol PM extract groups had significantly lower MDA concentrations in the brain after 18wk of feeding, indicating that the ethanol PM extracts were more ef fective for inhibiting lipid peroxidation.…”

Section: Dicussionmentioning

confidence: 99%

Beneficial Effects of Different Polygonum multiflorum Thunb. Extracts on Memory and Hippocampus Morphology

Chan

Cheng

Wang

2002

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryFour groups of 1-mo-old male senescence-accelerated mice (SAMP8) were fed Polygonum multiflorum Thunb. (PM) extract for 18wk to determine the effect of PM on memory ability and histopathological changes in mice. The baseline diet consisted of a ca sein diet group, and the three test diets were supplemented with 50% ethanol, 95% ethanol, or water extracts of PM. It was found that the mice fed with PM extracts had better active shuttle avoidance response, fewer vacuole numbers, less lipofuscin in the hippocampus, and lower MDA concentrations in the brain. Our data showed that the ethanol PM extract groups (both 50% and 95% groups) had lower lipofuscin percentages and MDA concentra tions, and higher total thiol concentrations than the water PM extract group. The 50% ethanol PM extract group showed significantly lower total cholesterol and triglyceride val ues than the other groups, but the HDL cholesterol level was the same. These results suggest that dietary supplementation with either ethanol or water extracts can reduce brain patho logical changes and promote learning and memory ability. The performance of PM extracts depended on the extraction method, with ethanol extraction tending to obtain better re sults.

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Role of lipid peroxidation and the glutathione‐dependent antioxidant system in the impairment of endothelium‐dependent relaxations with age

Cited by 45 publications

References 46 publications

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

A New, Potent Poly(ADP-ribose) Polymerase Inhibitor Improves Cardiac and Vascular Dysfunction Associated with Advanced Aging

Beneficial Effects of Different Polygonum multiflorum Thunb. Extracts on Memory and Hippocampus Morphology

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