The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA)

Nijveldt, Robert J.; Teerlink, Tom; Siroen, Michiel P. C.; Lambalgen, A.A. van; Rauwerda, J. A.; Leeuwen, Paul A. M. van

doi:10.1054/clnu.2002.0612

Cited by 141 publications

(119 citation statements)

References 41 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%

“…Unlike SDMA, which is entirely eliminated via renal excretion, ADMA is primarily metabolized to citrulline and dimethylamine by the liver enzyme dimethylarginine dimethylaminohydrolase. 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.…”

mentioning

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%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…Indeed, recent evidence does support a role for hepatic clearance of ADMA by DDAH. 21,22 Thus, with increased cholestatic liver damage there appears to be diminished capacity for hepatic ADMA metabolism contributing to increased circulatory levels, thereby perpetuating increased hepatic vascular tone.…”

mentioning

confidence: 99%

A gas, an amino acid, and an imposter: The story of nitric oxide, l-arginine, and ADMA in portal hypertension

Langer

Shah

2005

Hepatology

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The protection by heme oxygenase‐1 induction against thioacetamide‐induced liver toxicity is associated with changes in arginine and asymmetric dimethylarginine

Develi-İş

Bekpınar

Kalaz

et al. 2012

Cell Biochemistry & Function

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This study was designed to investigate the role of HO-1 induction in prevention of thioacetamide (TAA)-induced oxidative stress, inflammation and liver damage. The changes in hepatic dimethylarginine dimethylaminohydrolase (DDAH) activity as well as plasma arginine and asymmetric dimethylarginine (ADMA) levels were also measured to evaluate nitric oxide (NO) bioavailability. Rats were divided into four groups as control, hemin, TAA and hemin + TAA groups. Hemin (50 mg kg(-1) , i.p.) was injected to rats 18 h before TAA treatment to induce HO-1 enzyme expression. Rats were given TAA (300 mg kg(-1) , i.p.) and killed 24 h after treatment. Although TAA treatment produced severe hepatic injury, upregulation of HO-1 ameliorated TAA-induced liver damage up to some extent as evidence by decreased serum alanine transaminase, aspartate transaminase and arginase activities and histopathological findings. Induction of HO-1 stimulated antioxidant system and decreased lipid peroxidation in TAA-treated rats. Myeloperoxidase activity and inducible NO synthase protein expression were decreased, whereas DDAH activity was increased by hemin injection in TAA-treated rats. Induction of HO-1 was associated with increased arginine levels and decreased ADMA levels, being the main determinants of NO production, in plasma of TAA-treated rats. In conclusion, our results indicate that HO-1 induction alleviated increased oxidative stress and inflammatory reactions together with deterioration in NO production in TAA-induced liver damage in rats.

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The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA)

Cited by 141 publications

References 41 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

A gas, an amino acid, and an imposter: The story of nitric oxide, l-arginine, and ADMA in portal hypertension

The protection by heme oxygenase‐1 induction against thioacetamide‐induced liver toxicity is associated with changes in arginine and asymmetric dimethylarginine

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