Biochemical Evidence for Impaired Nitric Oxide Synthesis in Patients With Peripheral Arterial Occlusive Disease

Böger, Rainer H.; Bode‐Böger, Stefanie M.; W, Thiele; Junker, W.; Alexander, Klaus; Jc, Frölich

doi:10.1161/01.cir.95.8.2068

Cited by 457 publications

(287 citation statements)

References 36 publications

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“…This study is consistent with reports on increased circulating concentrations of ADMA in patients at risk or with vascular dysfunction or arteriosclerosis [7,10,13,25]. Serum concentrations of ADMA were approximately 20% higher in women with a history of GDM than in healthy women.…”

Section: Discussionsupporting

confidence: 92%

“…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%

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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: Discussionsupporting

confidence: 92%

mentioning

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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“…13 In patients with peripheral arterial occlusive disease, they also reported that there was a significantly progressive increase in plasma ADMA concentrations related to the severity of peripheral arterial occlusive disease. 14 Miyazaki et al reported that, in patients without any symptoms of CAD or peripheral arterial occlusive disease, plasma ADMA concentrations correlated positively with the risk factors for atherosclerosis, including age, glucose intolerance, and mean arterial pressure, and also correlated well with carotid intima-media thickness, an index of early atherosclerosis. 15 Moreover, Böger et al recently demonstrated that, also by inhibition of NO formation, ADMA stimulated the secretion of monocyte chemotactic protein-1, increased endothelial superoxide radical formation, and potentiated monocyte adhesion, which suggested that ADMA might be a proatherogenic molecule.…”

Section: Discussionmentioning

confidence: 99%

“…16,17 It may compete with L-arginine as the substrate for NO synthase, increase oxidative stress by uncoupling of electron transport between NO synthase and L-arginine, and hence decrease both the production and availability of endothelium-derived NO. 18 Elevations of ADMA level have been observed in urine from hypertensive rats, 19 in the regenerating endothelium of balloon-injured vessels, 20 and in plasma from patients with hypercholesterolemia, 13 congestive heart failure, 21 peripheral arterial occlusive disease, 14 essential hypertension, 22 and hypertriglyceridemia. 23 These reports suggested that elevation of ADMA might be involved in the pathogenesis of atherosclerosis.…”

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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“…It has been shown that by increasing plasma homocysteine concentrations using methionine infusion, FMD is impaired and this is associated with increased plasma ADMA [33]. Increased plasma concentrations of ADMA have also been described in a number of other conditions (Tables 1, 2) including diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia, hypertension, preeclampsia, stroke, peripheral vascular disease, congestive heart failure and acute coronary events [34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54]. Of interest, increased ADMA concentrations have also been implicated in the pathogenesis of conditions not affecting the cardiovascular system such as schizophrenia although the exact mechanism has yet to be clarified [55].…”

Section: Adma and Endothelial Dysfunction In Disease Statesmentioning

confidence: 99%

Asymmetric dimethylarginine (ADMA): a potential link between endothelial dysfunction and cardiovascular diseases in insulin resistance syndrome?

Chan

2002

Diabetologia

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Endothelium-derived nitric oxide plays a major role in the regulation of vascular tone and in the maintenance of vascular homeostasis. Endothelial dysfunction with impaired nitric oxide biosynthesis and decreased bioavailability has been implicated in insulin resistance syndrome and Type II (non-insulin-dependent) diabetes mellitus. Nitric oxide is synthesised by nitric oxide synthase. Asymmetric dimethylarginine is a major endogenous nitric oxide synthase inhibitor. Increased circulating asymmetric dimethylarginine was initially found in patients with chronic renal failure and subsequently many other disease states. Increased asymmetric dimethylarginine plasma concentrations could contribute to the development of insulin resistance and coronary heart disease. Understanding of the pathophysiological role of asymmetric dimethylarginine could lead to novel therapies in the prevention of arteriosclerosis and coronary heart disease. [Diabetologia (2002[Diabetologia ( ) 45:1609[Diabetologia ( -1616

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Biochemical Evidence for Impaired Nitric Oxide Synthesis in Patients With Peripheral Arterial Occlusive Disease

Abstract: In PAOD patients, there is a progressive reduction in urinary nitrate and cGMP excretion rates, which may be caused in part by accumulation of ADMA, an endogenous inhibitor of NO synthase.

Cited by 457 publications

References 36 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

Asymmetric dimethylarginine (ADMA): a potential link between endothelial dysfunction and cardiovascular diseases in insulin resistance syndrome?

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