HPLC determination of plasma dimethylarginines: Method validation and preliminary clinical application

Ivanova, Mariela; Artusi, Carlo Alberto; Boffa, Giovanni; Zaninotto, Martina; Plebani, Mario

doi:10.1016/j.cca.2010.06.001

Cited by 24 publications

(17 citation statements)

References 19 publications

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“…All of the T2DM patients had increased blood pressure, whereas five also had hypercholesterolemia compared with six and two nondiabetic control subjects, respectively. Experimental design, analytical measurements (20–22), calculations, and statistical analyses are available in the Supplementary Data.…”

Section: Methodsmentioning

confidence: 99%

Roles of Insulin, Age, and Asymmetric Dimethylarginine on Nitric Oxide Synthesis In Vivo

et al. 2013

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We tested the effects of insulin on production of nitrous oxide (NO)-related substances (nitrites and nitrates [NOx]) after 15N-arginine intravenous infusion and on asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations in conditions reportedly associated with altered NO availability, i.e., aging, hypertension, hypercholesterolemia, and type 2 diabetes mellitus (T2DM). A total of 26 male subjects (age 23–71 years, BMI 23–33 kg/m2), some of whom were affected by mixed pathologic features, were enrolled. NOx fractional synthesis rate (FSR) was lower in elderly (P < 0.015) and T2DM subjects (P < 0.03) than in matched control subjects. Hyperinsulinemia generally increased both NOx FSR and absolute synthesis rate (ASR) and reduced NOx, ADMA, and SDMA concentrations. Insulin sensitivity was impaired only in T2DM. With use of simple linear regression analysis across all subjects, age was inversely correlated with both NOx FSR (R2 = 0.23, P < 0.015) and ASR (R2 = 0.21, P < 0.02). NOx FSR inversely correlated with both ADMA and SDMA. With use of multiple regression analysis and various models, NOx FSR remained inversely associated with age and ADMA, whereas ASR was inversely associated with age and diabetes. No association with insulin sensitivity was found. We conclude that whole-body NOx production is decreased in aging and T2DM. Age, ADMA concentration, and T2DM, but not insulin resistance, appear as negative regulators of whole-body NOx production.

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Section: Methodsmentioning

confidence: 99%

Roles of Insulin, Age, and Asymmetric Dimethylarginine on Nitric Oxide Synthesis In Vivo

et al. 2013

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“…Each sample was collected predialysis, centrifuged, and frozen at 280°C, and it had not been previously thawed before testing. ADMA and L-arginine were measured by HPLC in batched assays at the University of Padua (17). Control samples were run with each batch to assess the reproducibility of test results.…”

Section: Measurement Of Admamentioning

confidence: 99%

Asymmetric Dimethylarginine, Race, and Mortality in Hemodialysis Patients

Drew¹,

Tighiouart

Scott

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race.Design, setting, participants, & measurements Asymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested.Results Mean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 mmol/L (0.16) versus 0.70 mmol/L (0.11) in African Americans (P,0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50).Conclusions African Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.

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“…The serum was kept frozen at -80°C until analysis. L-arginine, ADMA and SDMA, were measured by high performance liquid chromatography (HPLC) as previously described [ 22 , 23 ]. Assays were performed in duplicate.…”

Section: Methodsmentioning

confidence: 99%

Atrial Fibrillation Is Associated with a Marker of Endothelial Function and Oxidative Stress in Patients with Acute Myocardial Infarction

et al. 2015

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BackgroundAtrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI.Methods273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) ≥48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample.ResultsThe incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients without AF (≈ 20 y). There was a trend towards higher ADMA levels in patients with symptomatic AF than in patients with silent AF or no AF (0.53 vs 0.49 and 0.49 μmol/L, respectively, p = 0.18,). After matching on age, we found that patients with symptomatic AF had a higher heart rate on admission and a higher rate of patients with LV dysfunction (28% vs. 3%, p = 0.025). Patients who developed symptomatic AF had a higher ADMA level than patients without AF (0.53 vs. 0.43 μmol/L; p = 0.001). Multivariate logistic regression analysis to estimate symptomatic AF occurrence showed that ADMA was independently associated with symptomatic AF (OR: 2.46 [1.21–5.00], p = 0.013) beyond history of AF, LVEF<40% and elevated HR.ConclusionWe show that high ADMA level is associated with the occurrence of AF. Although no causative role can be concluded from our observational study, our work further supports the hypothesis that endothelial dysfunction is involved in the pathogenesis of AF in AMI.

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HPLC determination of plasma dimethylarginines: Method validation and preliminary clinical application

Cited by 24 publications

References 19 publications

Roles of Insulin, Age, and Asymmetric Dimethylarginine on Nitric Oxide Synthesis In Vivo

Roles of Insulin, Age, and Asymmetric Dimethylarginine on Nitric Oxide Synthesis In Vivo

Asymmetric Dimethylarginine, Race, and Mortality in Hemodialysis Patients

Atrial Fibrillation Is Associated with a Marker of Endothelial Function and Oxidative Stress in Patients with Acute Myocardial Infarction

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