Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit.

Cooke, John P.; Singer, Alan H.; Tsao, Philip S.; Zera, Pauline H.; Rowan, Reed A.; Billingham, Margaret E.

doi:10.1172/jci115937

Cited by 661 publications

(302 citation statements)

References 31 publications

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“…Several groups demonstrated that acute and chronic supplementation of L-arginine improves endothelial vasodilator responses in cholesterol fed animals and in patients with hypercholesterolemia and atherosclerosis [20][21][22][23]. Following these early studies, numerous studies with supplemental Larginine therapy have been conducted in animal models and in humans; however, no consistent results can be achieved [24••].…”

Section: Controversy Of L-arginine Supplemental Therapy In Atherosclementioning

confidence: 99%

Endothelial arginase: A new target in atherosclerosis

Yang

Ming

2006

Current Science Inc

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Section: Controversy Of L-arginine Supplemental Therapy In Atherosclementioning

confidence: 99%

Endothelial arginase: A new target in atherosclerosis

Yang

Ming

2006

Current Science Inc

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“…Supplementation with 2.25% L-arginine HO in the drinking water results in a sixfold enrichment of this amino acid (based on the daily average water and food intake of the animals) and induces a twofold increase in plasma arginine levels. 14 To determine if any effects of L-arginine supplementation were mediated by changes in caloric or nitrogen balance, a fourth group received a 1% cholesterol diet supplemented with 0.9% L-methionine (Met) in the drinking water to induce a sixfold increase in the daily intake of this amino acid.…”

Section: Animalsmentioning

confidence: 99%

“…14 To determine if this antiatherogenic effect of L-arginine doubled in the Arg group. There was no difference in maximum aggregation initiated by ADP (100 ^mol/L) between washed platelets from Con, Met, and Choi animals, but aggregation of platelets from Arg animals was significantly decreased (/ J <.05).…”

mentioning

confidence: 99%

L-arginine attenuates platelet reactivity in hypercholesterolemic rabbits.

Tsao

Theilmeier

Singer

et al. 1994

Arterioscler Thromb

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114

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Platelets are capable of producing nitric oxide (NO) through the L-arginine-NO synthase pathway. Acute exposure to supraphysiological concentrations of L-arginine in vitro increases the production of NO by platelets and is associated with an increase in platelet cyclic GMP (cGMP) levels and a reduction in platelet aggregation. The purpose of this study was to determine if chronic oral administration of L-arginine decreases platelet aggregation in hypercholesterolemic animals and to determine if this effect is mediated by the metabolism of L-arginine to NO. Male New Zealand White rabbits were fed normal chow (Con), a 1% cholesterol diet (Choi), or a 1% cholesterol diet supplemented with a sixfold enrichment of dietary L-arginine (Arg) or L-methionine (Met). After 10 weeks, cholesterol levels were equally increased in Choi and Arg animals, whereas plasma arginine levels were A therogenesis is thought to be initiated as a re-/\ sponse to injury of the endothelium. 1 This -Z. A. alteration of endothelial function favors platelet adherence and aggregation to the luminal surface, with the subsequent release of platelet-derived growth factors and vasoactive substances that contribute to the process of atherogenesis.One of the earliest alterations of the endothelium that has been observed in hypercholesterolemic animals and humans is decreased activity of endothelium-derived relaxing factor (EDRF). 24 EDRF is nitric oxide (NO) or a nitroso-containing compound derived from the metabolism of L-arginine by NO synthase. 58 This nitrovasodilator also inhibits platelet adhesion 9 and aggregation via the stimulation of intracellular guanylate cyclase to increase intracellular levels of cyclic GMP (cGMP). 1011 NO synthase and guanylate cyclase are also active in platelets, and platelet-derived NO autoregulates aggregation. 12 -13 A reduction in the activity of NO synthase by hypercholesterolemia could therefore lead to increased platelet-vessel wall interaction and enhanced atherogenesis.Recent studies in this laboratory have shown that chronic oral supplementation of the EDRF precursor L-arginine significantly improved NO-dependent vasodilation in hypercholesterolemic animals; this effect was associated with a striking reduction in intimal lesions. 14 To determine if this antiatherogenic effect of L-arginine Received August 13, 1993; revision accepted July 15, 1994 is associated with decreased platelet reactivity and enhancement of platelet-derived NO activity, we tested the hypothesis that (1) dietary L-arginine reduces platelet aggregation and (2) this effect is mediated by the metabolism of L-arginine to NO. Methods AnimalsMale New Zealand White rabbits received one of the following dietary interventions for 10 weeks: normal rabbit chow (Con), rabbit chow enriched with 1% cholesterol (Choi) (ICN Biomedical), or a 1% cholesterol chow supplemented with L-arginine (Arg) added to the drinking water throughout the course of the study. Supplementation with 2.25% L-arginine HO in the drinking water results in a sixfold e...

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“…A reduction in vascular availability of nitric oxide determines damage to endothelium-dependent vasodilatation, an increased tendency for platelet aggregation and adhesion of monocytes to the endothelium, and influences the proliferation of vascular smooth muscle cells, probably contributing to the onset and progression of atherosclerosis. In animal models of hypercholesterolemia, pharmacological inhibition of nitric oxide synthesis accelerates atherosclerosis 53 , but increased availability of nitric oxide decreases and may even lead to the regression of the disease 54,55 .…”

Section: Caramori and Zago Endothelial Dysfunction And Coronary Artermentioning

confidence: 99%