Nitric oxide and asymmetric dimethylarginine (ADMA) in malignancy associated thrombosis and their modulation by anticoagulants

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10573-10573
Author(s):  
J. Fareed ◽  
D. A. Hoppensteadt ◽  
M. Demir ◽  
O. Iqbal ◽  
W. Jeske ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Cancer Patients ◽  
Asymmetric Dimethylarginine ◽  
Oral Anticoagulants ◽  
Treated Group ◽  
Competitive Inhibitor ◽  
No Production ◽  
Open Label ◽  
Stage Renal Disease

10573 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. Plasma ADMA levels are upregulated in atherosclerosis, hypertension, end stage renal disease, chronic heart failure and microangiopathy. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n = 110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels by ELISA methods. Results: Both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However, in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA and NO. While E and W show a differential regulation of ADMA both result in downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.

Nitric oxide and asymmetric dimethylarginine and CD 40 ligand levels in malignancy associated thrombosis and their modulation by anticoagulants

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17049-17049
Author(s):  
D. Hoppensteadt ◽  
D. Fareed ◽  
O. Iqbal ◽  
A. Lale ◽  
J. Fareed
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Cancer Patients ◽  
Asymmetric Dimethylarginine ◽  
Oral Anticoagulants ◽  
Treated Group ◽  
Competitive Inhibitor ◽  
No Production ◽  
Open Label ◽  
Vasoactive Mediators

17049 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. CD 40 ligand (CD 40L) is also upregulated in cancer. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n=110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and CD 40L levels by ELISA methods. NO levels were measured using a chromogenic method. Results: The baseline levels of NO, ADMA and CD 40L levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA and CD 40L levels which persisted throughout the treatment period. However, in the W converted group the ADMA and CD 40L levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA, CD 40L and NO. While E and W show a differential regulation of ADMA and CD 40L, both result in a downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.

Nitric Oxide and Asymmetric Dimethlyarginine Levels in Malignancy Associated Thrombosis and Their Modulaiton by Anticoagulants.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1477-1477
Author(s):  
Debra Hoppensteadt ◽  
Daniel Fareed ◽  
Omer Iqbal ◽  
Ajit Lale ◽  
Jawed Fareed
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Cancer Patients ◽  
Treated Group ◽  
Competitive Inhibitor ◽  
Low Molecular Weight ◽  
No Production ◽  
Therapeutic Effects ◽  
Open Label ◽  
Down Regulation

Abstract Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at Pathophysiologic levels. While the association of ADMA in cardiovascular diseases is known, no information on the ADMA levels is available in cancer patients. To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were analyzed from an open label, multidose, active comparator designed study in which all patients (n=110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days. These patients were further subdivided. One group continued to receive E whereas the other group received warfarin (W) for up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels (Cardiovasics, Palo Alto, CA; R&D Systems, Minneapolis, MN, respectively). In comparison to the aged matched controls both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both enoxaparin and warfarin. These results suggest that patients with cancer and thrombosis exhibit simultaneous up regulation of ADMA and NO. While enoxaparin and warfarin show a differential regulation of ADMA both result in down regulation of NO. The fact that E regulates ADMA is highly suggestive of its regulatory role in iNOX which may be involved in the inflammatory response in cancer patients. Furthermore, these studies underscore the anti-inflammatory mechanisms by which low molecular weight heparins such as E, mediate their therapeutic effects in cancer asscoiated thrombosis. Group Nitric Oxide (uM) ADMA (uM) Aged matched controls 18±5 1.51±0.52 BL 63±18 5.34±1.5 IPE 22±9 2.81±0.9 4–6 weeks enoxaparin 20±8 2.45±0.9 4–6 weeks warfarin 25±8 3.67±1.1

scholarly journals Indolent course of tubulointerstitial disease in a mouse model of subpressor, low-dose nitric oxide synthase inhibition

2008 ◽  
Vol 295 (3) ◽  
pp. F717-F725 ◽  
Author(s):  
Adelina Stoessel ◽  
Alexander Paliege ◽  
Franziska Theilig ◽  
Francesco Addabbo ◽  
Brian Ratliff ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Basement Membrane ◽  
Mouse Model ◽  
Asymmetric Dimethylarginine ◽  
In Vivo Model ◽  
No Production ◽  
Collagen Xviii

Deficiency of nitric oxide (NO) represents a consistent manifestation of endothelial dysfunction (ECD), and the accumulation of asymmetric dimethylarginine occurs early in renal disease. Here, we confirmed in vitro and in vivo the previous finding that a fragment of collagen XVIII, endostatin, was upregulated by chronic inhibition of NO production and sought to support a hypothesis that primary ECD contributes to nephrosclerosis in the absence of other profibrotic factors. To emulate more closely the indolent course of ECD, the study was expanded to an in vivo model with NG-monomethyl-l-arginine(l-NMMA; mimics effects of asymmetric dimethylarginine) administered to mice in the drinking water at subpressor doses of 0.3 and 0.8 mg/ml for 3–6 mo. This resulted in subtle but significant morphological alterations detected in kidneys of mice chronically treated with l-NMMA: 1) consistent perivascular expansion of interstitial matrix components at the inner stripe of the outer medulla and 2) collagen XVIII/endostatin abundance. Ultrastructural abnormalities were detected in l-NMMA-treated mice: 1) increased activity of the interstitial fibroblasts; 2) occasional detachment of endothelial cells from the basement membrane; 3) splitting of the vascular basement membrane; 4) focal fibrosis; and 5) accumulation of lipofuscin by interstitial fibroblasts. Preembedding labeling of microvasculature with anti-CD31 antibodies showed infiltrating leukocytes and agglomerating platelets attaching to the visibly intact or denuded capillaries. Collectively, the data indicate that the mouse model of subpressor chronic administration of l-NMMA is not a robust one (endothelial pathology visible only ultrastructurally), and yet it closely resembles the natural progression of endothelial dysfunction, microvascular abnormalities, and associated tubulointerstitial scarring.

scholarly journals Uncoupling of Vascular Nitric Oxide Synthase Caused by Intermittent Hypoxia

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammad Badran ◽  
Bisher Abuyassin ◽  
Saeid Golbidi ◽  
Najib Ayas ◽  
Ismail Laher
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Intermittent Hypoxia ◽  
Asymmetric Dimethylarginine ◽  
Chronic Intermittent Hypoxia ◽  
No Production ◽  
Diabetic Mice ◽  
Enos Uncoupling ◽  
Obstructive Sleep ◽  
Oxide Synthase

Objective. Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is often present in diabetic (DB) patients. Both conditions are associated with endothelial dysfunction and cardiovascular disease. We hypothesized that diabetic endothelial dysfunction is further compromised by CIH.Methods. Adult male diabetic (BKS.Cg-Dock7m+/+Leprdb/J) (db/db) mice (10 weeks old) and their heterozygote littermates were subjected to CIH or intermittent air (IA) for 8 weeks. Mice were separated into 4 groups: IA (intermittent air nondiabetic), IH (intermittent hypoxia nondiabetic), IADB (intermittent air diabetic), and IHDB (intermittent hypoxia diabetic) groups. Endothelium-dependent and endothelium-independent relaxation and modulation by basal nitric oxide (NO) were analyzed using wire myograph. Plasma 8-isoprostane, interleukin-6 (IL-6), and asymmetric dimethylarginine (ADMA) were measured using ELISA. Uncoupling of eNOS was measured using dihydroethidium (DHE) staining.Results. Endothelium-dependent vasodilation and basal NO production were significantly impaired in the IH and IADB group compared to IA group but was more pronounced in IHDB group. Levels of 8-isoprostane, IL-6, ADMA, and eNOS uncoupling were ≈2-fold higher in IH and IADB groups and were further increased in the IHDB group.Conclusion. Endothelial dysfunction is more pronounced in diabetic mice subjected to CIH compared to diabetic or CIH mice alone. Oxidative stress, ADMA, and eNOS uncoupling were exacerbated by CIH in diabetic mice.

scholarly journals Dimethylarginine – biomarkers in progression of kidney disease / Dimetilarginini – biomarkeri u progresiji bubrežnih oboljenja

2012 ◽  
Vol 31 (4) ◽  
pp. 301-308 ◽  
Author(s):  
Tatjana Cvetković ◽  
Radmila Pavlović ◽  
Vidosava Đorđević ◽  
Ivana Stojanović ◽  
Radmila Veličković-Radovanović ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Competitive Inhibitor ◽  
No Production ◽  
Uremic Toxin ◽  
Strong Positive Correlation ◽  
Progression Of Kidney Disease ◽  
Arginine Residues ◽  
Dimethyl Arginine

Summary Decreased nitric oxide (NO) production and/or impaired NO bioavailability may occur in patients with the chronic kidney disease (CKD), and could contribute to elevation of blood pressure, cardiovascular disease (CVD) and progression of renal injury in these patients. Free guanidinomethylated arginine residues occur endogenously as a result of proteolysis of post-translational methylated tissue proteins. The asymmetric dimethyl arginine (ADMA) is a competitive inhibitor of the nitric oxide synthase (NOS) enzymes. The kidney has a predominant role in ADMA elimination by combining two mechanisms; urinary excretion and metabolization of ADMA The degradation of ADMA is accomplished intracellularly by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). ADMA is not only a uremic toxin, but also a strong marker of the endothelial dysfunction and atherosclerosis and a stronger independent predictor of all-cause mortality and cardiovascular outcome in patients with the chronic renal failure. There are at least four mechanisms that may explain the accumulation of ADMA in CKD: increased methylation of proteins, increased protein turnover, decreased metabolism by DDAH and impaired renal excretion. A strong positive correlation between symmetric dimethyl arginine (SDMA) and creatinine suggests that SDMA might be of value as a marker of the renal function. Reduced NO elaboration secondary to accumulation of ADMA and elevated inflammation may be important pathogenic factors for endothelial dysfunction in patients with the renal disease. Elevation of ADMA may be a missing link between CVD and CKD.

Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

2007 ◽  
Vol 293 (2) ◽  
pp. R707-R713 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Barbara K. Kemp-Harper ◽  
Helena C. Parkington ◽  
Geoffrey A. Head ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Arterial Pressure ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
No Production ◽  
Wild Type ◽  
Early Diabetes ◽  
Diabetes In Mice ◽  
Vehicle Treatment

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of Nω-nitro-l-arginine methyl ester (l-NAME; 100 mg·kg−1·day−1 in drinking water; 97 ± 3 mmHg) than after vehicle treatment (88 ± 3 mmHg). MAP was also elevated in eNOS null mice (113 ± 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in l-NAME-treated mice (108 ± 5 mmHg) but not in vehicle-treated mice (88 ± 3 mmHg) nor eNOS null mice (104 ± 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic l-NAME or induction of diabetes but was reduced by 42 ± 6% in l-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by l-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.

Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication

2007 ◽  
Vol 97 (03) ◽  
pp. 444-450 ◽  
Author(s):  
Rino Migliacci ◽  
Alessandra Procacci ◽  
Paola De Monte ◽  
Erminio Bonizzoni ◽  
Paolo Gresele
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Intermittent Claudication ◽  
Treadmill Exercise ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Lower Limbs ◽  
Exercise Induced ◽  
Induced Changes ◽  
Ncx 4016

SummaryIschemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day I (pre-treatment: aspirin = 3.1 ± 0.5%, nitroaspirin = 3.9 ± 0.7%, p=NS), and on day 28 (aspirin = 3.4 ± 0.7%, NCX 4016 = 3.2 ± 0.6%, p=NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = –1.15%, nitroaspirin = –1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirin-treated group (- 1.46%) while it was abolished in the NCX 4016-treated group (+ 0.79%, p= 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-l which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction.

Hypoxia inhibits nitric oxide synthesis in isolated rabbit lung

1997 ◽  
Vol 272 (6) ◽  
pp. L1167-L1173 ◽  
Author(s):  
S. P. Kantrow ◽  
Y. C. Huang ◽  
A. R. Whorton ◽  
E. N. Grayck ◽  
J. M. Knight ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Competitive Inhibitor ◽  
Oxidation Products ◽  
No Oxidation ◽  
Severe Hypoxia ◽  
No Production ◽  
Rabbit Lung ◽  
Vasoconstrictor Response ◽  
Hypoxic Vasoconstriction ◽  
Oxide Synthase

Nitric oxide (NO.) has been proposed to modulate hypoxic vasoconstriction in the lung. The activity of nitric oxide synthase (NOS) can be inhibited by hypoxia because molecular oxygen is a necessary substrate for the enzyme. On the basis of this mechanism, we hypothesized that NOS activity has a key role in regulation of pulmonary vascular tone during hypoxia. We measured oxidation products of NO. released into the vasculature of isolated buffer-perfused rabbit lung ventilated with normoxic (21% O2), moderately hypoxic (5% O2), or anoxic (0% O2) gas using two methods. Mean PO2 in perfusate exiting the lung was 25 Torr during anoxic ventilation and 47 Torr during moderately hypoxic ventilation. We found that the amount of the NO. oxidation product nitrite released into the perfusate was suppressed significantly during ventilation with anoxic but not moderately hypoxic gas. During normoxic ventilation, nitrite release was inhibited by pretreatment with NG-monomethyl-L-arginine, a competitive inhibitor of NOS. To confirm that changes in nitrite concentration reflected changes in NO. release into the perfusate, major oxidation products of NO. (NOx) were assayed using a method for reduction of these products to NO. by vanadium(III) Cl. Release of NOx into the perfusate was suppressed by severe hypoxia (anoxic ventilation), and this effect was reversed by normoxia. Pulmonary vasoconstriction was observed during severe but not moderate hypoxia and was related inversely to the rate of nitrite release. These observations provide evidence that decreased NO. production contributes to the pulmonary vasoconstrictor response during severe hypoxia.

Adenosine enhances nitric oxide production by vascular endothelial cells

1995 ◽  
Vol 269 (2) ◽  
pp. C519-C523 ◽  
Author(s):  
J. M. Li ◽  
R. A. Fenton ◽  
B. S. Cutler ◽  
J. G. Dobson
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Vascular Tone ◽  
Vascular Endothelial Cells ◽  
Competitive Inhibitor ◽  
No Production ◽  
Dependent Manner ◽  
Bathing Medium ◽  
Adenosine Receptor Antagonist ◽  
Potent Vasodilator

Adenosine per se is a potent vasodilator of vascular smooth muscle. Endothelial cells modulate vascular tone via the release of nitric oxide (NO), which also elicits vasodilation. This study was undertaken to determine whether adenosine could directly stimulate endothelial cells to enhance NO production, which could subsequently reduce vascular tone. NO production was evaluated in porcine carotid artery endothelial cells (PCAEC) and human saphenous vein endothelial cells (HSVEC) seeded on multiwell plates, grown to confluence, and treated with adenosine for 1 h. The bathing medium was collected, and the NO production was determined as reflected by the formation of NO2- and NO3-. NO production by PCAEC was significantly increased by adenosine in a dose-dependent manner, whereas there was only an insignificant tendency for an increase by HSVEC. The addition of the NO synthase competitive inhibitor, NG-monomethyl-L-arginine (NMMA), or the adenosine receptor antagonist, theophylline, prevented the increase in NO production by adenosine. The results suggest that adenosine stimulates, by a receptor-mediated mechanism, the production of NO by arterial, but not by venous, endothelial cells.

scholarly journals Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA) Concentrations in Patients with Obesity and the Risk of Obstructive Sleep Apnea (OSA)

2019 ◽  
Vol 8 (6) ◽  
pp. 897 ◽  
Author(s):  
Yana Arlouskaya ◽  
Ada Sawicka ◽  
Marek Głowala ◽  
Joanna Giebułtowicz ◽  
Natalia Korytowska ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Asymmetric Dimethylarginine ◽  
Apnea Hypopnea Index ◽  
Enos Gene ◽  
No Production ◽  
Serum Concentrations ◽  
Symmetric Dimethylarginine ◽  
Obstructive Sleep

Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of nitric oxide (NO) synthesis, and play a critical role in the process of endothelial dysfunction, and are considered markers of oxidative stress. The aim of the present study was to explore relationships between ADMA and/or SDMA and the occurrence of OSA in obese patients as well as the effect of the endothelial nitric oxide synthase (eNOS) gene polymorphism, which may modify the influence of ADMA or SDMA on NO production. A total of 518 unrelated obese subjects were included in this study. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Obstructive sleep apnea (OSA) was assessed by the apnea hypopnea index (AHI). Blood samples were collected to measure serum concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, creatinine, HbA1c (%), folic acid, vitamin B12, C-reactive protein (CRP), aspartate aminotransferase (ASP), alanine aminotransferase (ALT) and IL-6 by routine methods. The NOS3 gene G894T and 4a/4b polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. ADMA, SDMA and arginine concentrations were assessed simultaneously using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method. Adjusted multivariate logistic regression analysis showed a significant association between the occurrence of OSA and high serum ADMA levels, BMI above 40, age > 43 years, hypertension and male sex. Heterozygotes for the G894T eNOS polymorphism have the lowest serum concentrations of ADMA and SDMA, while no effect of the 4a/4b variants was observed. The results indicate that OSA in obese individuals can coexist with high ADMA levels, which appear as a potential OSA predictor.

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