Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality

Nijveldt, Robert J.; Teerlink, Tom; Hoven, Ben van der; Siroen, Michiel P. C.; Kuik, D.J.; Rauwerda, Jan A.; Leeuwen, Paul A. M. van

doi:10.1054/clnu.2002.0613

Cited by 229 publications

(203 citation statements)

References 28 publications

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“…13,14 In this study, we investigated whether ADMA may be related to intrahepatic endothelial dysfunction. Plasma ADMA levels were increased only in rats with biliary cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

“…Separation of these amino acids was achieved via reversed phase high-performance liquid chromatography according to Teerlinck and colleagues. 13,14,22 Samples were spiked with known amounts of these amino acids for identification of peaks, recovery, and quantitation. A calibration curve (over the range 1-20 nmol ADMA) was constructed; the detection limit was 200 pmol/L.…”

Section: Methodsmentioning

confidence: 99%

“…12,13 Accordingly, it has been suggested that impaired liver function leads to increased plasma levels of ADMA. 13,14 Several recent studies have linked ADMA to endothelial dysfunction and cardiovascular disease, such as arterial hypertension, and multiorgan failure. 12,14 However, the specific intrahepatic hemodynamic effects of ADMA remain unclear.…”

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confidence: 99%

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A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

Laleman¹,

Omasta²,

Casteele³

et al. 2005

Hepatology

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Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis. Two rat models of cirrhosis (thioacetamide [TAA]-induced and bile duct excision [BDE]-induced, n ‫؍‬ 10 each), one rat model of PHT without cirrhosis (partial portal vein-ligated [PPVL], n ‫؍‬ 10), and sham-operated control rats (n ‫؍‬ 10) were studied. We assessed hepatic NOS activity, eNOS protein expression, plasma ADMA levels, and intrahepatic endothelial function. To evaluate intrahepatic endothelial function, concentration-effect curves of acetylcholine were determined in situ in perfused normal rat livers and livers of rats with TAAor BDE-induced cirrhosis (n ‫؍‬ 10) that had been preincubated with either vehicle or ADMA; in addition, measurements of nitrite/nitrate (NOx) and ADMA were made in perfusates. Both models of cirrhosis exhibited decreased hepatic NOS activity. In rats with TAA-induced cirrhosis, this decrease was associated with reduced hepatic eNOS protein levels and immunoreactivity. Rats with BDE-induced cirrhosis had eNOS protein levels comparable to those in control rats but exhibited significantly higher plasma ADMA levels than those in all other groups. In normal perfused liver, ADMA induced impaired endothelium-dependent vasorelaxation and reduced NOx perfusate levels, phenomena that were mimicked by N G -nitro-L-arginine-methyl ester. In contrast to perfused livers with cirrhosis induced by TAA, impaired endothelial cell-mediated relaxation in perfused livers with cirrhosis induced by BDE was exacerbated by ADMA and was associated with a decreased rate of removal of ADMA (34.3% ؎ 6.0% vs. 70.9% ؎ 3.2%). In conclusion, in rats with TAA-induced cirrhosis, decreased eNOS enzyme levels seem to be responsible for impaired NOS activity; in rats with biliary cirrhosis, an endogenous NOS inhibitor, ADMA, may mediate decreased NOS activity. (HEPATOLOGY 2005;42:1382-1390

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“…13,14 In this study, we investigated whether ADMA may be related to intrahepatic endothelial dysfunction. Plasma ADMA levels were increased only in rats with biliary cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

Laleman¹,

Omasta²,

Casteele³

et al. 2005

Hepatology

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“…In animals, a high-fat, high-cholesterol diet increases SDMA serum levels (19,20) without affecting renal function (20), indicating that cardiovascular risk factors other than impaired renal function can influence SDMA plasma levels. Furthermore, in intensive care patients, elevated SDMA correlated much better with the total sequential organ failure assessment score than ADMA and indicated both renal and hepatic failure (21).…”

mentioning

confidence: 88%

Symmetrical Dimethylarginine

Bode‐Böger

Scalera

Kielstein

et al. 2006

Journal of the American Society of Nephrology

253

204

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Symmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine. Whereas the major route of asymmetric dimethylarginine elimination is the hydrolytic degradation by dimethylarginine dimethylaminohydrolase, SDMA is eliminated by renal excretion. SDMA does not directly inhibit NOS but is a competitor of arginine transport. This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD). In 97 patients with CAD, SDMA was a marker of estimated GFR. On multiple regression analysis of the CAD parameter stenosis score, SDMA was the only parameter retained. In addition, endothelial cells from the third passage were cultured in medium that contained 70 mol/L arginine and was incubated for 24 h in the presence of various concentration of SDMA (0, 2, 5, 10, and 100 mol/L). The levels of nitrate and nitrite in conditioned media, the protein expression of NOS, and the content of reactive oxygen species in endothelial cells were determined. SDMA inhibited dose dependently the NO synthesis in intact endothelial cells, whereas it had no effect on protein expression of NOS. This effect was associated with an increase in reactive oxygen species. Co-incubation with S ymmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). ADMA has been shown to correlate with risk factors for coronary artery disease (CAD) such as hypertension (1,2), hypercholesterolemia (3), hyperhomocysteinemia (4 -6), insulin resistance (7), age (1), and mean arterial pressure (1). Moreover, ADMA correlates with the extent and the severity of coronary atherosclerosis (8) and is a strong and independent marker of cardiovascular events and mortality in selected patient populations (9 -11). Although there is mounting evidence that chronically elevated ADMA may contribute to progression of vascular disease via endothelial damage, little attention has been paid to the role of SDMA. Both ADMA and SDMA derive from intranuclear methylation of l-arginine residuals and are released into the cytoplasm after proteolysis (12). SDMA is produced by protein-arginine methyltransferase 5 (PRMT 5) and PRMT 7 (both type II methyltransferases) (13,14). Only ADMA but not SDMA is metabolized by dimethylarginine dimethylaminohydrolase to citrulline and dimethylamine (15). SDMA seems to be strictly eliminated by renal excretion (16,17). A recent study by Fliser et al. (18) showed a very close correlation among serum creatinine, GFR (measured by iodothalamate clearance technique), and SDMA. The authors speculated that SDMA, equal to serum creatinine, can serve as a marker of renal function, but SDMA seems to be more than a simple indicator of renal function. In animals, a high-fat, high-cholesterol diet increases SDMA serum levels (19,20) without affecting renal function (20), indicating that cardiovascular risk factors other than impaired...

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“…Kritik hastalığı olan ve kardiyojenik şok tablosundaki hastalarda, ADMA'nın kötü prognozla ilişkili olduğu kabul edilmektedir (30) .…”

Section: B-4 Adma-konjestif Kalp Yetmezliğiunclassified

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2012

Okmeydani Medical Journal

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Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality

Cited by 229 publications

References 28 publications

A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

Symmetrical Dimethylarginine

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