Putative mechanisms of the impairment of endothelium-dependent relaxation of the aorta with atheromatous plaque in heritable hyperlipidemic rabbits.

Tagawa, Hirofumi; Tomoike, Hitonobu; Nakamura, Motoomi

doi:10.1161/01.res.68.2.330

Cited by 72 publications

(29 citation statements)

References 42 publications

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“…Vessels from Chol-fed rabbits did not differ in their response to an EC-independent vasodilator, in agreement with other investigators (21), suggesting that the ability of VSMCs to relax is intact. Other reports propose that impaired ECdependent relaxation is due to L-arginine depletion, the substrate for NO synthesis (3,12,13).…”

Section: Discussionsupporting

confidence: 91%

“…19], a critical event in development of the atherosclerotic lesion (20). In addition, reactive oxygen species have been implicated in the alterations of EC-dependent relaxation observed in atherosclerosis (21,22 Vessel Contraction Studies. New Zealand White rabbits (2.5-3.0 kg) were maintained on rabbit chow containing 1% cholesterol (Ralston Purina) for 6 months prior to study [cholesterol-fed (Chol-fed) group].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Superoxide and peroxynitrite inatherosclerosis.

White

Brock

Chang

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

658

370

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The role of reactive oxygen species in the vascular pathology asiated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (NO) with superoxide (O2), yielding the oxidant peroynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet Endothelium-dependent relaxation is impaired in vessels from atherosclerotic patients (1, 2) and hypercholesterolemic animal models (3-6), suggesting the functional modification of endothelium-derived relaxing factor (EDRF) in hyperlipidemia. The dynamic role ofthe endothelium in the regulation of vascular tone was established when it was observed that relaxation of isolated blood vessels by vasoactive agents, such as acetylcholine (ACh) and the calcium ionophore A23187, was dependent on an intact endothelium and a diffusible factor (EDRF) that stimulated cGMP-dependent relaxation of vascular smooth muscle cells (VSMCs; ref. 7).Nitric oxide (-NO) and EDRF share similar chemical and pharmacological properties (8) and are derived from the oxidation of a terminal guanidino group of L-arginine (9, 10).Numerous mechanisms have been suggested for the defect in vascular relaxation in atherosclerosis and hypercholesterolemic animal models. They include an increased diffusional barrier for 'NO due to intimal cell proliferation and lipid deposition (11), L-argifine depletion (3,12,13) Vessel Contraction Studies. New Zealand White rabbits (2.5-3.0 kg) were maintained on rabbit chow containing 1% cholesterol (Ralston Purina) for 6 months prior to study [cholesterol-fed (Chol-fed) group]. Age-and weight-matched controls were fed a standard diet. After exsanguination under ketamine/rompun anesthesia, vessels were isolated and changes in tension were measured in femoral artery ring segments as described (28). After maximal contraction with 70 mM KCl and recovery, phenylephrine was added to achieve 30% of maximal tone. Rings were then exposed to increasing doses of ACh; relaxation is reported as the percentage decrease in preexisting tone. After the generation of cumulative ACh dose-response curves, rings were exposed to 30 ,uM papaverine. In some experiments, rings from control and Chol-fed rabbits were incubated with 3 mM L-arginine for 30 min prior to administration of ACh. In other studies, vessels were treated with native bovine SOD (200 units/ml) before measuring ACh-induced relaxation. All studies were performed in the presence of 5 !uM indomethacin.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Superoxide and peroxynitrite inatherosclerosis.

White

Brock

Chang

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

658

370

View full text Add to dashboard Cite

show abstract

“…Similarly, endothelium-dependent vasorelaxant responses to acetylcholine and )thelium-dethrombin are attenuated in iliac arteries excised from cynomoltance vessels gus monkeys with diet-induced atherosclerosis (31 The precise mechanism by which hypercholesterolemia impairs endothelium-dependent vasodilation is not known. Po- 3 10 tential explanations for this phenomenon include reduced synthesis or release ofEDRF, increased degradation ofEDRF, and tin) competing vasoconstrictive stimuli (35)(36)(37)(38) (40)(41)(42)47). Normal responses return after the administration of L-arginine.…”

Section: Discussionmentioning

confidence: 99%

L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.

Creager¹,

Gallagher²,

Girerd³

et al. 1992

J. Clin. Invest.

731

320

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Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76±0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65±0.36 mmol/ liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor. (J. Clin.

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“…35 Endothelial function appears impaired in the microcirculation as well as in large arteries of atherosclerotic animals and humans. 36 These findings suggest that oxidative stress could be involved in the mechanisms of vascular disorders and AD.…”

Section: Hanon Et Al Arterial Stiffness and Cognitive Function 2195mentioning

confidence: 96%

Relationship Between Arterial Stiffness and Cognitive Function in Elderly Subjects With Complaints of Memory Loss

Hanon

Haulon

Lenoir

et al. 2005

Stroke

237

176

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Background and Purpose-To evaluate the relationship between arterial stiffness and cognitive function in a population of elderly subjects reporting memory loss. Methods-We studied the association between cognitive function and arterial stiffness in 308 consecutive elderly subjects attending a geriatric outpatient clinic reporting memory impairment. Subjects were classified into 4 categories according to neuropsychological evaluation: normal cognitive function, mild cognitive impairment (MCI), Alzheimer disease (AD), or vascular dementia (VaD). Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) measurement using Complior. Results-In this population, 78Ϯ8 years of age (women 64%), AD was present in 41%, VaD in 6%, MCI in 27%, and 26% of subjects had normal cognitive function. After adjustment for age, gender, systolic blood pressure, education level, cardiovascular diseases, and antihypertensive therapy, a significant association was observed between PWV and cognitive status (PϽ0.0001). PWV appears significantly higher in subjects with VaD (15.2Ϯ3.9 m/s) or AD (13.3Ϯ2.9 m/s) than in those without cognitive impairment (11.5Ϯ2.0 m/s; PϽ0.001). Moreover, PWV was higher in subjects with MCI (12.6Ϯ2.6 m/s) than in those without cognitive impairment (11.5Ϯ2.0 m/s; Pϭ0.01). For each 2 m/s increment in PWV, the adjusted odds ratio (95% CI) was 1.

show abstract

Putative mechanisms of the impairment of endothelium-dependent relaxation of the aorta with atheromatous plaque in heritable hyperlipidemic rabbits.

Cited by 72 publications

References 42 publications

Superoxide and peroxynitrite inatherosclerosis.

Superoxide and peroxynitrite inatherosclerosis.

L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.

Relationship Between Arterial Stiffness and Cognitive Function in Elderly Subjects With Complaints of Memory Loss

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