Effects of Dietary
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            -Arginine on Atherosclerosis and Endothelium-Dependent Vasodilatationin the Hypercholesterolemic Rabbit

Jeremy, Richmond W.; McCarron, Hugh C. K.; Sullivan, David

doi:10.1161/01.cir.94.3.498

Cited by 95 publications

(74 citation statements)

References 57 publications

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“…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••]. In recent years, there has been an increasing number of studies showing either no effect or no sustained effects on endothelial function by L-arginine supplementation [6,[25][26][27][28][29][30]. Harmful effects on atherosclerotic lesion formation in ApoE/iNOS double-knockout mice have been reported [31].…”

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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“…Subjects were excluded if they had: any disease process, other than peripheral arterial disease, limiting treadmill exercise capacity; evidence of arterial disease of a non-atherosclerotic nature; undergone major surgery in the previous 3 months; a leg amputation above the ankle; suffered a myocardial infarction in the previous 3 months; type I diabetes; uncontrolled hypertension (Ͼ180 systolic or Ͼ100 diastolic); a current malignancy; significantly impaired renal or hepatic function; or if they were currently enrolled in another clinical trial. Subjects were required to discontinue certain products affecting peripheral vessels Vascular Medicine 2000; 5: [11][12][13][14][15][16][17][18][19] specifically pentoxifylline, carnitine, prostacyclin analogs or l-arginine 28 days prior to acquiring baseline data. Subjects were otherwise asked to continue their regular medications, diet and lifestyle habits and were free to follow any other medical care regimens.…”

Section: Subjectsmentioning

confidence: 99%

“…In patients with hypercholesterolemia and/or atherosclerosis, the impairment of EDNO synthesis can be reversed by administration of l-arginine. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] Likewise, in patients with coronary and peripheral arterial diseases, administration of l-arginine enhances EDNO synthesis, improves endothelium-dependent vasodilation and ameliorates the symptoms of angina and intermittent claudication. [19][20][21] However, the beneficial effects of l-arginine have been observed with intravenous administration or high doses (6-21 g/day) of oral supplementation.…”

Section: Introductionmentioning

confidence: 99%

Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar®

2000

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Abstract:We investigated the clinical effects of a food bar enriched with l-arginine and a combination of other nutrients known to enhance the activity of endothelium-derived nitric oxide (EDNO) in individuals with claudication from atherosclerotic peripheral arterial disease. The study was a 2-week, double-blind, placebo-controlled trial of subjects randomized to three groups (two active bars, one active and one placebo bar, and two placebo bars per day) followed by an 8-week open-label period. Subjects (n = 41) were outpatient volunteers with intermittent claudication. Pain-free and total walking distances were measured by variable-grade, treadmill exercise testing. Quality of life was assessed using the Medical Outcome Survey (SF-36). After 2 weeks of treatment, the pain-free walking distance increased 66% while the total walking distance increased 23% in the group taking two active bars/day. The general and emotional/social functioning components of the SF-36 also improved. These effects were not observed in the one active bar/day and placebo groups. The effects were maintained after 10 weeks and, in addition, an improvement in walking distance was observed in the group taking one active bar. These findings reveal that use of a nutrient bar designed to enhance EDNO activity improves pain-free and total walking distance as well as quality of life in individuals with intermittent claudication.

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“…Numerous reports indicate the utility of L-arginine supplementation to enhance NO biosynthesis in several vascular diseases; [14][15][16][17]30,31 however, there have been conflicting negative studies. 32,33 Although there are many factors influencing the outcome of L-arginine supplementation in vascular disorders, the degree of intracellular L-arginine elevation may limit its biological effects. We now report an alternative and exceedingly efficient mode of delivering Larginine into vascular tissue and this approach could also be useful for enhancing delivery of L-arginine to the endothelium under conditions where L-arginine may be rate-limiting.…”

Section: Discussionmentioning

confidence: 99%

Short Polymers of Arginine Rapidly Translocate Into Vascular Cells

Uemura

Rothbard

Matsushita

et al. 2002

Circ J

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ascular nitric oxide (NO) is synthesized from its precursor L-arginine by endothelial cells and contributes to vascular relaxation as well as maintenance of normal vascular structure. 1,2 Vascular NO inhibits monocyte adherence and chemotaxis, 3 platelet adherence and aggregation 4,5 and proliferation of vascular smooth muscle cells (VSMC). 6 The vascular endothelium normally express endothelial NO synthase (eNOS), but in certain disease states, vascular cells also express inducible NO synthase (iNOS). Recent evidence suggests that preservation or enhancement of NO synthesis can prevent or reverse some of the pathophysiological processes that contribute to vascular proliferative diseases.Because the intracellular levels of L-arginine far exceed the Km of the NOS enzyme, NO synthesis is ordinarily not dependent on extracellular supplementation, 7 but under certain circumstances, local L-arginine concentration can become rate-limiting, as with elevated plasma or tissue concentrations of the endogenous NO synthase antagonist ADMA (asymmetric dimethylarginine) 8,9 or in the context of inflammation and expression of the inducible NO synthase (iNOS). 10,11 Both of these abnormalities operate in the setting of vascular injury, 12,13 in which we and others have demonstrated that oral, intravenous or local supplementation of L-arginine enhances NO synthesis and beneficially modulates vascular function and structure, including the atherosclerosis and myointimal formation after vascular injury. [14][15][16][17] Recently, we observed that short polymers of arginine Circulation Journal Vol.66, December 2002(heptamers or greater) rapidly translocate through the cytoplasmic and nuclear membranes of vascular cells in a very efficient manner. 18 Furthermore, we have shown that pretreatment of a vascular segment with short polymers of arginine inhibits myointimal formation after vein grafting. 19 Although the mechanisms are still unclear, these polymers seem to translocate through the cytoplasmic membrane independently of the classical basic amino acid transport system. The present study was performed to extend these findings to vascular cells and in particular, to characterize the transport of L-arginine polymers and their effect on NO biosynthesis in cytokine-stimulated VSMC in culture. We chose those cells to study because after angioplasty, they rather than endothelial cells become the major source of NO production in the vessel wall. Methods ReagentsPeptides were synthesized using solid-phase techniques and commercially available Fmoc amino acids, resins, and reagents (PE Biosystems, Foster City, CA, and Bachem, Torrence, CA, USA) on an Applied Biosystems 433 peptide synthesizer as previously described. 20 The reagents used were: (a) penta-L-arginine (R5: NH2-RRRRR-CONH2, R = L-arginine), (b) hepta-L-arginine (R7: NH2-RRRRRRR-COOH), (c) nona-L-arginine (R9: NH2-RRRRRRRRR-COOH), (d) hepta-D-arginine (D-r7: NH2-rrrrrrr-COOH), (e) biotinylated R7 (bR7: biotin-Aca-RRRRRRR-CONH2), and (f) biotinylated hepta-L-lysine (bK7: biotin-...

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Effects of Dietary l -Arginine on Atherosclerosis and Endothelium-Dependent Vasodilatationin the Hypercholesterolemic Rabbit

Cited by 95 publications

References 57 publications

Endothelial arginase: A new target in atherosclerosis

Endothelial arginase: A new target in atherosclerosis

Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar®

Short Polymers of Arginine Rapidly Translocate Into Vascular Cells

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