Plasma Concentrations of Asymmetric Dimethylarginine, an Endogenous Nitric Oxide Synthetase Inhibitor, Are Elevated in Sickle Cell Patients but Do Not Increase during Painful Crises.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3795-3795
Author(s):  
Pearl Landburg ◽  
Tom Teerlink ◽  
Sigrid de Jong ◽  
Frits A. Muskiet ◽  
Ashley J. Duits ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell ◽  
Asymmetric Dimethylarginine ◽  
Plasma Concentrations ◽  
Endothelial Activation ◽  
Healthy Controls ◽  
Asymptomatic Patients ◽  
Plasma Adma ◽  
One Way Anova ◽  
Painful Crisis

Abstract Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenously produced inhibitor of nitric oxide (NO) synthase, are elevated and related to endothelial activation in clinically asymptomatic patients with sickle cell disease (SCD). However, ADMA concentrations have not been defined during acute vaso-occlusive complications. We determined plasma ADMA and arginine concentrations in 96 samples (40 collected in the clinically asymptomatic state and 56 collected at presentation with a painful crisis) of 44 HbSS patients (mean age 32±13 years, m:f=23:21) and in 39 samples (22 collected in the clinically asymptomatic state and 17 collected at presentation with a painful crisis) of 22 HbSC patients (mean age 30±14 years, m:f=10:12). Thirty-five race, sex and age matched HbAA blood donors served as healthy controls. Plasma ADMA concentrations were elevated in asymptomatic sickle cell patients as compared to healthy controls (HbSS: mean 0.7±0.1 umol/L, HbSC mean 0.5±0.1 umol/L, HbAA mean 0.4±0.1 umol/L; p<0.001 one way ANOVA). Plasma arginine concentrations were lower in asymptomatic HbSS patients as compared to asymptomatic HbSC patients and healthy controls (HbSS: mean 59.6±25.8 umol/L, HbSC mean 75.5±25.8 umol/L, HbAA mean 74.0±27.1 umol/L; p=0.03 one way ANOVA). Ratio’s of ADMA to arginine (ADMA/Arginine × 1000) were highest in HbSS patients (HbSS: mean 16.2±11.6, HbSC mean 7.8±2.9, HbAA mean 6.3±3.2; p=0.001 one way ANOVA). In both HbSS and HbSC patients, neither ADMA (p=0.17/p=0.57), arginine (p=0.13/p=0.18) nor the ADMA/arginine ratio (p=0.88/p=0.08) differed between the asymptomatic phase and at presentation with a painful crisis. In conclusion, even though ADMA is elevated in SCD and therefore may well be involved in the development of chronic organ complications by limiting NO availability, ADMA concentrations are not affected during acute painful sickle cell crises.

Measurement of Urine Pyridinoline and Deoxypyridinoline as Markers of Increased Bone Degradation in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2572-2572
Author(s):  
Erfan Nur ◽  
Willem Mairuhu ◽  
Dees P. Brandjes ◽  
Ton van Zanten ◽  
Bart J. Biemond ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Bone Resorption ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Healthy Controls ◽  
Cell Disease ◽  
Skeletal Involvement ◽  
Asymptomatic Patients ◽  
Bone Degradation ◽  
Painful Crisis

Abstract Abstract 2572 Poster Board II-549 Introduction: Sickle cell disease (SCD) is commonly manifested through skeletal involvement. Besides the characteristic acute musculoskeletal pain, SCD is also associated with chronic skeletal complications such as osteopenia and osteoporosis. During bone resorption, the collagen cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are released into circulation with subsequent urinary excretion. Measurements of urinary PYD and DPD could serve as valuable tools in detecting osteoporosis in the follow-up of SCD patients but perhaps also in determining the severity of bone infarction during painful crises. Therefore we compared urinary concentrations of PYD and DPD of SCD patients during asymptomatic state and painful crisis with those of race- and age-matched healthy controls. Methods: Urinary concentrations of PYD and DPD, adjusted for urine creatinine, were measured in SCD patients both during asymptomatic state (n=38) and painful crisis (n=27) and healthy controls with normal HbA hemoglobin (n=25) using high performance liquid chromatography (HPLC). Results: PYD and DPD concentrations were higher in asymptomatic SCD patients compared to controls ((54.8 (41.5–68.6) vs. 44.1 (37.7–49.9),P=0.005 and 11.6 (9.3–15.2) vs. 8.5 (6.8–10.4),P=0.004 respectively), with further increments during painful crisis (63.3 (51.8–76.0),P=0.041 and 15.3(13.0–21.5),P=0.003 respectively). In the asymptomatic patients levels of PYD and DPD were significantly correlated to the degree of hemolysis. Conclusion: In sickle cell patients bone resorption is increased and significantly correlated to the degree of hemolysis, compatible with their susceptibility to osteopenia and osteoporosis. Measurement of pyridinoline and deoxypyridinoline could have additional value as biomarkers of osteoporosis in SCD. During painful crises a further increment in bone degradation was observed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery

2012 ◽  
Vol 49 (6) ◽  
pp. 589-594 ◽  
Author(s):  
R Patle ◽  
S Dubb ◽  
J Alaghband-Zadeh ◽  
R A Sherwood ◽  
F Tam ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Asymmetric Dimethylarginine ◽  
Obese Patients ◽  
Endogenous Inhibitor ◽  
Nitrite Concentration ◽  
Plasma Adma ◽  
Adma Concentration

Background Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery. Methods Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. Results Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg ( P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg ( P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 μmol/L ( P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 μmol/L ( P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant ( P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO. Conclusions After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO–ADMA axis. Other causes for the changes in BP should therefore be considered.

scholarly journals The Role of Nitric Oxide, ADMA, and Homocysteine in The Etiopathogenesis of Preeclampsia—Review

2019 ◽  
Vol 20 (11) ◽  
pp. 2757 ◽  
Author(s):  
Weronika Dymara-Konopka ◽  
Marzena Laskowska
Keyword(s):  
Nitric Oxide ◽  
Asymmetric Dimethylarginine ◽  
Disease Process ◽  
Endothelial Activation ◽  
Morbidity And Mortality ◽  
Clinical Implications ◽  
Target Tissue ◽  
Vessel Involvement

Preeclampsia is a serious, pregnancy-specific, multi-organ disease process of compound aetiology. It affects 3–6% of expecting mothers worldwide and it persists as a leading cause of maternal and foetal morbidity and mortality. In fact, hallmark features of preeclampsia (PE) result from vessel involvement and demonstrate maternal endothelium as a target tissue. Growing evidence suggests that chronic placental hypoperfusion triggers the production and release of certain agents that are responsible for endothelial activation and injury. In this review, we will present the latest findings on the role of nitric oxide, asymmetric dimethylarginine (ADMA), and homocysteine in the etiopathogenesis of preeclampsia and their possible clinical implications.

Coronary Flow Reserve and Asymmetric Dimethylarginine Levels: New Measurements for Identifying Subclinical Atherosclerosis in Patients with Psoriatic Arthritis

2011 ◽  
Vol 38 (8) ◽  
pp. 1661-1664 ◽  
Author(s):  
FABIOLA ATZENI ◽  
PIERCARLO SARZI-PUTTINI ◽  
SIMONA SITIA ◽  
LIVIO TOMASONI ◽  
LUIGI GIANTURCO ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Coronary Flow Reserve ◽  
Coronary Flow ◽  
Asymmetric Dimethylarginine ◽  
Subclinical Atherosclerosis ◽  
Clinical Manifestations ◽  
Healthy Controls ◽  
Carotid Imt ◽  
Flow Reserve ◽  
Plasma Adma

Objective.To identify the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) and healthy controls using intima-media thickness (IMT), coronary flow reserve (CFR), and the plasma concentration of asymmetric dimethylarginine (ADMA), to evaluate the correlations among ADMA, IMT, and CFR.Methods.The study involved 22 patients who fulfilled the ClASsification of Psoriatic ARthritis study group criteria for PsA and a cohort of 35 healthy controls with no history or current signs of coronary artery disease (CAD). Common carotid IMT was measured using high-resolution B-mode ultrasonography. Dipyridamole transthoracic stress echocardiography was used to evaluate CFR. Blood samples were obtained to assess ADMA levels. The clinical manifestations were recorded. All patients were treated with disease-modifying antirheumatic drug, but none had received any biological or steroid therapy.Results.Plasma ADMA levels were significantly higher in the patients with PsA (0.71 ± 0.07 μmol/l vs 0.48 ± 0.07 μmol/l; p = 0.00) and CFR was significantly reduced in that group (2.86 ± 0.70 vs 3.3 ± 0.43; p < 0.01) compared to controls. Common carotid IMT was greater in the patients with PsA, but the difference was not significant (0.64 ± 0.26 mm vs 0.62 ± 0.5 mm; p = 0.65). There was a significant correlation between CFR and plasma ADMA levels in the PsA group (R = 0.28; p < 0.01), but no correlation between plasma ADMA levels and IMT (R = 0.02; p = 0.32), Disease Activity Score 28 (p = 0.52), or Psoriasis Area and Severity Index (p = 0.98).Conclusion.Our patients with PsA showed a profile of subclinical atherosclerosis. ADMA may be a useful marker of endothelial dysfunction in PsA.

scholarly journals Asymmetric dimethylarginine in angiotensin II-induced hypertension

2010 ◽  
Vol 298 (3) ◽  
pp. R740-R746 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Natasha C. Moningka ◽  
Mark W. Cunningham ◽  
Byron Croker ◽  
Chris Baylis
Keyword(s):  
Nitric Oxide ◽  
Renal Injury ◽  
Asymmetric Dimethylarginine ◽  
Renal Cortex ◽  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Plasma Adma ◽  
Induced Hypertension

Recent studies have shown that asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor, is increased in hypertension and chronic kidney disease. However, little is known about the effects of hypertension per se on ADMA metabolism. The purpose of this study was to test the hypothesis that ANG II-induced hypertension, in the absence of renal injury, is associated with increased oxidative stress and plasma and renal cortex ADMA levels in rats. Male Sprague-Dawley rats were treated with ANG II at 200 ng·kg−1·min−1 sc (by minipump) for 1 or 3 wk or at 400 ng·kg−1·min−1 for 6 wk. Mean arterial pressure was increased after 3 and 6 wk of ANG II; however, renal injury (proteinuria, glomerular sclerosis, and interstitial fibrosis) was only evident after 6 wk of treatment. Plasma thiobarbituric acid reactive substances concentration and renal cortex p22phox protein abundance were increased early (1 and 3 wk), but urinary excretion of isoprostane and H2O2 was only increased after 6 wk of ANG II. An increased in plasma ADMA after 6 wk of ANG II was associated with increased lung protein arginine methyltransferase-1 abundance and decreased renal cortex dimethylarginine dimethylaminohydrolase activity. No changes in renal cortex ADMA were observed. ANG II hypertension in the absence of renal injury is not associated with increased ADMA; however, when the severity and duration of the treatment were increased, plasma ADMA increased. These data suggest that elevated blood pressure alone, for up to 3 wk, in the absence of renal injury does not play an important role in the regulation of ADMA. However, the presence of renal injury and sustained hypertension for 6 wk increases ADMA levels and contributes to nitric oxide deficiency and cardiovascular disease.

Effect of acute variations of insulin and glucose on plasma concentrations of asymmetric dimethylarginine in young people with Type 1 diabetes

2008 ◽  
Vol 115 (12) ◽  
pp. 361-369 ◽  
Author(s):  
M. Loredana Marcovecchio ◽  
Barry Widmer ◽  
David B. Dunger ◽  
R. Neil Dalton
Keyword(s):  
Type 1 Diabetes ◽  
Risk Factor ◽  
Young People ◽  
Asymmetric Dimethylarginine ◽  
Plasma Concentrations ◽  
Young Patients ◽  
Glucose Levels ◽  
Significant Fall ◽  
Plasma Adma

ADMA (asymmetric dimethylarginine), an endogenous inhibitor of nitric oxide synthase, is considered a major risk factor for cardiovascular disease and progression of renal disease. In the present study we aim to investigate the effect of acute variations in plasma glucose and insulin on plasma ADMA levels in young people with T1D (Type 1 diabetes). Fifteen young patients (ten males) with T1D, median age 18.3 (13.2–24.4) years, HbA1c (glycated haemoglobin) 9% (6.4–13.6%), underwent an overnight (18:00–08:00 hours) variable insulin infusion for euglycaemia, followed by a hyperinsulinaemic–euglycaemic clamp (08:00–12:00 hours). Blood samples were collected every 15 min for determination of ADMA, SDMA (symmetric dimethylarginine), valine, phenylalanine, arginine, creatinine and glucose. Insulin levels were assessed every 30 min. During the overnight period, glucose levels increased following the evening meal. In response to the protein intake there was a significant increase in ADMA, arginine, valine, phenylalanine and creatinine. For the remaining part of the night, glucose levels progressively decreased reaching 5 mmol/l by 04:00 hours. ADMA and SDMA did not change significantly. During the hyperinsulinaemic clamp, a significant fall in ADMA was observed, from 0.468±0.056 to 0.364±0.050 μmol/l (P<0.001). A significant fall was also found in SDMA, valine, phenylalanine, arginine and the ADMA/SDMA ratio (all P<0.001), but not in creatinine levels. No correlation was found between insulin sensitivity and ADMA. We conclude that acute changes in glycaemia do not significantly affect plasma ADMA levels whereas infusion of insulin significantly reduces ADMA, suggesting an important role for insulin in the regulation of this cardiovascular risk factor.

Circulating Endothelial Cells: A Potential Parameter of Organ Damage in Sickle Cell Anemia?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4798-4798
Author(s):  
Michiel Strijbos ◽  
Precious Landburg ◽  
Erfan Nur ◽  
Bart J. Biemond ◽  
Frank Leebeek ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Disease Severity ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Endothelial Activation ◽  
Organ Damage ◽  
Circulating Endothelial Cells ◽  
Laboratory Markers ◽  
Leukocyte Counts ◽  
Painful Crisis

Abstract Traditional laboratory markers of disease severity (Hb concentrations, HbF%, LDH concentrations and leukocyte counts) are not powerful enough to identify individuals with sickle cell disease (SCD) at high risk of complications. In several disease states, the number of circulating endothelial cells (CEC) is indicative of the extent of vascular disease and several small studies employing cumbersome techniques have shown increased CEC to occur in SCD as well. In this pilot study we determined if, by employing the CellSearch system, elevated CEC can be detected in SCD and whether the CEC count is related to the presence of organ damage, painful crisis frequency, traditional laboratory markers of disease severity as well as markers of endothelial activation. Peripheral blood was collected from 15 sickle cell patients and 15 healthy sex, age and race matched HbAA controls. Cells positive for CD146 (present on endothelial cells) are immuno-magnetically isolated and stained with nuclear DAPI and anti-CD105 (present on endothelial cells) and anti-CD45 (pan-leukocyte marker). Within the CD146 enriched cell suspension, cells meeting the DAPI+/CD146+/CD105+/CD45− criteria after image cytometry are designated CEC. CEC counts were significantly higher in sickle cell patients (12 cells/mL, IQR 8–29) as compared to controls (4 cells/mL, 3–10) (p=0.007). CEC counts were significantly higher in patients with pulmonary hypertension (PHT) (p=0.02), and increased with the presence of number of affected organs as well (0–4 involved organs, p=0.03), with the number of affected organs being the most important determinant of increased CEC numbers in SCD (R2=0.72, P=0.001). No statistically significant correlation was detected between CEC counts and markers of endothelial activation (serum sVCAM-1 and plasma VWF:Ag levels). CEC counts did not differ between patients on hydroxyurea and those who did not use hydroxyurea. No statistically significant correlations were detected between CEC counts and painful crisis frequency, Hb, HbF%, leukocyte counts, LDH concentrations. In conclusion, elevated CEC’s can be demonstrated in the clinically asymptomatic state in patients with sickle cell anemia with a validated and automated technique and, for the first time, a relation of CEC counts to SCD related organ damage is demonstrated. Furthermore, the extent of EC activation (as assessed by sVCAM-1 and VWF:Ag levels) is not necessarily related to the extent of EC damage (as assessed by CEC counts).

Sign in / Sign up

Export Citation Format

Share Document