Elevatedl-Arginine/Dimethylarginine Ratio Contributes to Enhanced Systemic NO Production by Dietaryl-Arginine in Hypercholesterolemic Rabbits

Bode‐Böger, Stefanie M.; Böger, Rainer H.; Kienke, Sven; Junker, W.; Jc, Frölich

doi:10.1006/bbrc.1996.0279

Cited by 290 publications

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“…It was previously suggested that the key determinant of NOS activity is provided by the balance between ADMA and L-arginine, as reflected in the L-arginine to ADMA ratio, 13 rather than the concentration of the individual markers. 7,14 We found that at 11 --13 weeks in pregnancies that subsequently develop early PE both the ratios of L-arginine to ADMA and L-homoarginine to ADMA are reduced with consequent likely decrease in NOS activity.…”

Section: Discussionmentioning

confidence: 88%

“…12 The ratio of L-arginine to ADMA is associated with altered NOS activity 13 and is a useful index for evaluating the effects of ADMA. 7,14 NO, along with its substrates and inhibitors, is thought to have an important role in the pathophysiology of preeclampsia (PE), which is characterized by widespread vasoconstriction. Several studies have reported that in PE the maternal plasma concentration of ADMA is increased, whereas the concentration of L-arginine is decreased, increased or normal.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric dimethylarginine, arginine and homoarginine at 11–13 weeks’ gestation and preeclampsia: a case–control study

et al. 2011

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The aim of this study was to investigate whether the nitric oxide (NO) pathway is altered in pregnancies that develop preeclampsia (PE). This was a nested case --control study of screening for PE, in which plasma asymmetric dimethylarginine (ADMA), L-arginine and L-homoarginine were measured at 11 þ 0 --13 þ 6 weeks. In all, 75 pregnancies that developed PE, including 25 requiring delivery before 34 weeks (early PE), and 300 unaffected controls were included. L-arginine and L-homoarginine were measured by gas chromatography-mass spectrometry, whereas ADMA was measured by gas chromatography-tandem mass spectrometry. Multiple regression analysis was used to determine if any maternal characteristics or gestation were significant predictors. In the early-PE group, both L-arginine and L-homoarginine expected medians (MoMs) were significantly reduced (median, IQR: 0.85, 0.76 --1.04 vs 0.98, 0.88 --1.16, P ¼ 0.021 and 0.78, 0.65 --0.96 vs 0.99, 0.77 --1.31, P ¼ 0.006, respectively) but ADMA MoMs were not significantly different (P ¼ 0.599). In early PE, compared with controls, the ratios of ADMA to L-arginine MoMs and ADMA to L-homoarginine MoMs were increased (median, IQR: 1.19, 0.94 --1.33 vs 1.01, 0.75 --1.31, P ¼ 0.003 and 1.21, 0.93 --1.61 vs 0.99, 0.87 --1.16, P ¼ 0.012, respectively). There were no significant differences between late PE and controls in ADMA, L-arginine, L-homoarginine or their ratios. In conclusion, development of early PE is associated with altered NO metabolism and/or synthesis apparent from the first trimester.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Asymmetric dimethylarginine, arginine and homoarginine at 11–13 weeks’ gestation and preeclampsia: a case–control study

et al. 2011

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“…A decreased plasma L-arginine to ADMA ratio or increased ADMA concentrations has been described in hypercholesterolemia [6,7], hypertension [8,9], arterial occlusive disease [10], chronic renal failure [11], and preeclampsia [12]. It has been suggested that alteration of the L-arginine to ADMA ratio could affect the clinical course of arteriosclerosis, which has not been seen in patients with stable angina [13].…”

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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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“…The systemic clearance of ADMA occurs upon catalytic hydrolysis by the dimethylarginine dimethylaminohydrolase (DDAH) to L-citrulline and dimethylamine (DMA), membrane transport by SLC7 family members, and urinary excretion of ADMA as well as DMA [194,195]. A correlation between ADMA plasma levels and the severity of disease has been suggested as an analytical reference for disease risk factors [196].…”

Section: Asymmetric Dimethylarginine (Adma)-adma Is a Biogenic Analogmentioning

confidence: 99%

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

Boudko

2007

Journal of Chromatography B

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This review briefly summarizes recent progress in fundamental understanding and analytical profiling of the L-arginine/nitric oxide (NO) pathway. It focuses on key analytical references of NO actions and on the experimental acquisition of these references in vivo, with capillary electrophoresis (CE) and high-performance capillary electrophoresis (HPCE) comprising one of the most flexible and technologically promising analytical platform for comprehensive high-resolution profiling of NO-related metabolites. Second aim of this review is to express demands and bridge efforts of experimental biologists, medical professionals and chemical analysis-oriented scientists who strive to understand evolution and physiological roles of NO and to develop analytical methods for use in biology and medicine.

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Elevatedl-Arginine/Dimethylarginine Ratio Contributes to Enhanced Systemic NO Production by Dietaryl-Arginine in Hypercholesterolemic Rabbits

Cited by 290 publications

References 0 publications

Asymmetric dimethylarginine, arginine and homoarginine at 11–13 weeks’ gestation and preeclampsia: a case–control study

Asymmetric dimethylarginine, arginine and homoarginine at 11–13 weeks’ gestation and preeclampsia: a case–control study

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

Bioanalytical profile of the l-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis

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