Restoring vascular nitric oxide formation by l-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease

Böger, Rainer H.; Bode‐Böger, Stefanie M.; W, Thiele; Creutzig, A; Alexander, Klaus; Frölich, Jürgen C.

doi:10.1016/s0735-1097(98)00375-1

Cited by 233 publications

(134 citation statements)

References 38 publications

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“…A power calculation based on results in the control group estimates that a difference between means as small as 0.1 µmol/l is detectable with 80% power. It is currently unclear if ADMA could also be used as a surrogate endpoint in clinical trials as suggested from studies in patients with peripheral artery disease receiving intravenous L-arginine therapy [38] or in insulin-resistant patients receiving the insulin sensitizer rosiglitazone [19]. Since specific mimetics or inhibitors of intracellular methyltransferases are also not available at present, it will be difficult to extrapolate clinical findings to ADMA concentrations.…”

Section: Discussionmentioning

confidence: 99%

Circulating concentrations of asymmetrical dimethyl- L -arginine are increased in women with previous gestational diabetes

Mittermayer

Meyer

et al. 2002

Diabetologia

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Aims/hypothesis. The concentration of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, is increased in patients at risk or with cardiovascular disease. We have investigated ADMA concentrations in women with a history of gestational diabetes (GDM), who could develop endothelial dysfunction and Type II (non-insulin-dependent) diabetes mellitus after delivery, and in healthy control subjects. Methods. Previous GDM patients were grouped according to their BMI as obese (≥25 kg/m 2 , n=46) or non-adipose (<25 kg/m 2 , n=31). Serum samples were taken 14 to 16 weeks after delivery and after 1 year. The control group comprised 17 healthy women (BMI<25 kg/m 2 ). ADMA concentrations were analysed by high performance liquid chromatography. Results. ADMA concentrations were comparable between obese and non-adipose GDM patients (0.58±0.02 and 0.57±0.02 µmol/l, respectively), and higher than in the control group (0.47±0.03 µmol/l; p<0.006). Insulin resistance as estimated by the insulin sensitivity index was more frequent among the obese than the non-adipose GDM women (p<0.05) and control subjects (p<0.05, both). No change in ADMA concentrations was found after 1 year in women with GDM. There was only a slight correlation between ADMA and BMI (r=0.26, p<0.02), triglycerides (r=0.29, p<0.004), or fasting plasma glucose (r=0.21, p<0.05), and not with the insulin sensitivity index or other parameters. In a multiple regression analysis ADMA serum concentrations were only associated with triglycerides. Conclusion/interpretation. Circulating ADMA concentrations are increased in normoglycaemic women with previous GDM. This increase is independent from other risk factors or surrogate markers for diabetes or cardiovascular events. [Diabetologia (2002[Diabetologia ( ) 45:1372[Diabetologia ( -1378 Keywords Gestational diabetes, asymmetrical dimetylarginine, nitric oxide, insulin resistance, cholesterol. . L-arginine can also be methylated by intracellular methyltransferases [3], but the exact regulation of this pathway is not known. The methylated L-arginine metabolite, asymmetrical dimethyl-L-arginine (ADMA), inhibits the cellular L-arginine uptake and nitric oxide synthase activity in endothelial cells competitively [4]. The allosteric symmetrical dimethyl-L-arginine (SDMA) is produced in equivalent amounts, but is not a structural antagonist in nitric oxide synthesis [5].It has been speculated that accumulation of endogenous L-arginine metabolites and low availability of LNitric oxide is synthesized from the amino acid L-arginine by constitutive and inducible nitric oxide synthases [1] and plays an important role in the regulation

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Section: Discussionmentioning

confidence: 99%

Circulating concentrations of asymmetrical dimethyl- L -arginine are increased in women with previous gestational diabetes

Mittermayer

Meyer

et al. 2002

Diabetologia

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“…Moreover, the restoration of endothelial function by supplementation of L-arginine also suggested that competitive inhibition of NO synthase pathway might be one of the important mechanisms. 13,24 However, the relation between ADMA and CAD has not been well investigated. Recently, two studies have shown that plasma ADMA level is both an independent risk factor of cardiovascular mortality in patients undergoing hemodialysis and a predictor of acute coronary events in middle-aged men.…”

Section: Introductionmentioning

confidence: 99%

Asymmetrical dimethylarginine: A novel risk factor for coronary artery disease

Ding

Charng

et al. 2003

Clinical Cardiology

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SummaryBackground: Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and has been associated with systemic atherosclerosis; however, the role of ADMA in patients with coronary artery disease (CAD) has not been investigated.Hypothesis: The present study was designed to determine whether the plasma ADMA level predicts the presence of CAD independently, and whether the plasma ADMA level correlates with the extent and severity of coronary atherosclerosis.Methods: In all, 97 consecutive patients with angina and positive exercise stress test were enrolled prospectively for coronary angiography. According to the result of angiography, the subjects were divided into two groups: Group 1 (n = 46): patients with normal coronary artery or mild CAD (< 50% stenosis of major coronary arteries); Group 2 (n = 51): patients with significant CAD (≥ 50% stenosis of major coronary arteries). Plasma levels of ADMA and L-arginine were determined by high-performance liquid chromatography. In addition, we used coronary atherosclerotic score to assess the extent and severity of CAD.Results: The plasma levels of ADMA in Group 2 patients were significantly higher than those in Group 1 patients (0.66

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“…Passados 30 minutos, após da infusão de 30g de arginina, foi observado que sua concentração no plasma aumentou para aproximadamente 7.000μmol.L -1 (24) . Diversos estudos avaliaram o efeito da infusão de arginina em pacientes apresentando doenças cardiovasculares (25) , hipercolesteronemia (26) , hipertensão (27) , diabetes (28) e comprometimentos vasculares periféricos (29) , e, em todas as circunstâncias, a infusão de arginina aumentou a produção/função do NO.…”

Section: Discussionunclassified

Suplementação proteica não aumenta a concentração plasmática de óxido nítrico em homens saudáveis

Moraes

Aoki²,

Araújo

et al. 2009

Rev Bras Med Esporte

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Suplementos nutricionais, supostamente, capazes de potencializar a produção endógena de óxido nítrico (NO) têm experimentado crescente popularidade entre os indivíduos fisicamente ativos. Diante da carência de informações sobre o assunto, o objetivo do presente estudo foi avaliar o efeito de um suplemento comercial à base de proteínas e aminoácidos sobre a produção endógena de NO. Métodos: A amostra foi constituída de 12 homens sedentários, mas sem fatores de risco para doenças cardiovasculares. O protocolo de suplementação foi conduzido conforme o arranjo experimental duplo-cego cruzado. ABSTRACTNutritional supplements, theoretically able to increase endogenous nitric oxide (NO) production have experienced great popularity among physically active individuals. Aim: scientific evidence available regarding this issue is scarce. Therefore, the purpose of this study was to evaluate the effect of a dietary supplement commercialized as a nitric oxide booster. Materials and methods: twelve sedentary men with no risk factors for cardiovascular diseases were supplemented with placebo or protein in two different occasions. The present study was conducted in a cross double-blind design. In order to assess plasmatic NO concentration, blood samples were obtained before (24hs and immediately before) and after (30 and 60 minutes) consumption of placebo (PLA) or protein supplement (SP INTRODUÇÃOOs mecanismos responsáveis pela hipertrofia muscular, em resposta ao treinamento de força, não estão, totalmente, elucidados (1) . Estudos recentes sugerem que esse tipo de exercício promove o acúmulo de substâncias (ex.: lactato) no meio intra e extracelular, que seriam capazes de desencadear a ativação do sistema simpático e a liberação de hormônios hipofisários (2,3) . O acúmulo desses metabólitos seria responsável por traduzir a sobrecarga utilizada no treinamento em estímulo para a síntese proteica adaptativa (4) . Vale ressaltar que não existem estudos que relacionem o efeito das alterações agudas no perfil hormonal/metabólico em resposta ao treino de força e a adaptação crônica (longo prazo) induzida por esse tipo de treinamento físico (2) . Nesse contexto, várias teorias foram elaboradas para explicar como essas respostas agudas estimulariam a hipertrofia do músculo esquelético. Considerando os possíveis mecanismos fisiológi-cos envolvidos nesse processo, alguns autores propuseram a hipótese da supercirculação. Esta sugere que o incremento do fluxo sanguíneo para o músculo seria um dos estímulos que poderiam potencializar a hipertrofia (5) . No caso do treinamento de força, esse aumento na circulação ocorreria, predominantemente, ao término do exercício. Essa resposta resultaria em maior aporte de nutrientes e hormônios para o músculo, bem como a remoção acelerada de subprodutos do metabolismo.O NO é um vasodilatador endógeno que tem sido investigado, com crescente interesse, devido a seu possível envolvimento nos efeitos cardioprotetores promovidos pelo exercício (6) . Com base na hipótese da supercirculação, suplementos nutri...

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Restoring vascular nitric oxide formation by l-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease

Abstract: Restoring NO formation and endothelium-dependent vasodilation by L-arginine improves the clinical symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.

Cited by 233 publications

References 38 publications

Circulating concentrations of asymmetrical dimethyl- L -arginine are increased in women with previous gestational diabetes

Circulating concentrations of asymmetrical dimethyl- L -arginine are increased in women with previous gestational diabetes

Asymmetrical dimethylarginine: A novel risk factor for coronary artery disease

Suplementação proteica não aumenta a concentração plasmática de óxido nítrico em homens saudáveis

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