Asymmetric dimethylarginine (ADMA) determines the improvement of hepatic endothelial dysfunction by vitamin E in cirrhotic rats

Authors

  • Ying-Ying Yang,

    Corresponding author
    1. Department of Medicine, National Yang-Ming University School of Medicine,, Taipei, Taiwan
    • Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital,, Taipei, Taiwan
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  • Tzung-Yan Lee,

    1. Graduate Institute of Traditional Chinese Medicine, Chang Gung University,, Taipei, Taiwan
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  • Yi-Tsau Huang,

    1. Institute of Traditional Medicine, National Yang-Ming University School of Medicine,, Taipei, Taiwan
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  • Che-Chang Chan,

    1. Department of Medicine, National Yang-Ming University School of Medicine,, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital,, Taipei, Taiwan
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  • Yi-Chen Yeh,

    1. Department of Medicine, National Yang-Ming University School of Medicine,, Taipei, Taiwan
    2. Department of pathology, Taipei Veterans General Hospital,, Taipei, Taiwan
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  • Fa-Yauh Lee,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital,, Taipei, Taiwan
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  • Shou-Dong Lee,

    1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital,, Taipei, Taiwan
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  • Han-Chieh Lin

    Corresponding author
    1. Department of Medicine, National Yang-Ming University School of Medicine,, Taipei, Taiwan
    2. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital,, Taipei, Taiwan
    • Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital,, Taipei, Taiwan
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Correspondence

Han-Chieh Lin, MD, Professor, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan and Ying-Ying Yang, MD, PhD, Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan

Tel: +886 2 28757506

Fax: +886 2 28739318

e-mail: hclin@vghtpe.gov.tw; yangyy@vghtpe.gov.tw

Abstracts

Background

Hepatic endothelial dysfunction (HED), which is caused by decreased hepatic nitric oxide (NO) bioavailability and increased lipid peroxidation, contributes to portal hypertension, which is a characteristic of cirrhosis. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is involved in cirrhosis-related HED and portal hypertension.

Aims

We evaluated the effect of vitamin E treatment on the lipid peroxidation, HED and portal hypertension in cirrhotic rats.

Methods

The common bile duct ligation (BDL)-induced cirrhotic rats were treated orally either with vehicle or with vitamin E for 1 month immediately after BDL. Systemic and portal haemodynamics, the magnitude of the increase in portal pressure induced by volume expansion, HED, oxidative stress, levels of ADMA, various proteins and mRNAs were then measured.

Results

In the vitamin E-treated BDL rats, a decrease in portal pressure was associated with an attenuation of the increased portal pressure induced by volume expansion. In isolated and perfused BDL rat livers, the vitamin E treatment significantly inhibited the (paradoxical) vasoconstriction response to methoxamine and acetylcholine (HED), and this was abolished by the presence of NOS. Vitamin E decreased ADMA synthesizing enzyme PRMT1 expression and the level of thiobarbituric acid-reactive substances (TBARS) in the liver, while increasing the levels of hepatic ADMA metabolizing enzyme DDAH2, eNOS, phosphor-eNOS, ADMA level and superoxide dismutase activity.

Conclusions

The administration of vitamin E suppressed hepatic ADMA and oxidative stress in the cirrhotic liver circulation, and therefore increases NO bioavailability, which improved HED and portal hypertension.

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