Basal release of nitric oxide in the mesenteric artery in portal hypertension and cirrhosis: Role of dimethylarginine dimethylaminohydrolase

Authors

  • Eva Serna,

    1. Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
    2. Institute of Health Research INCLIVA, Valencia, Spain
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    • These authors contributed equally to this work and share first authorship.
  • María Dolores Mauricio,

    1. Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
    2. Institute of Health Research INCLIVA, Valencia, Spain
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    • These authors contributed equally to this work and share first authorship.
  • Paloma Lluch,

    1. Hepatology Unit, Valencia, Spain
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  • Gloria Segarra,

    1. Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
    2. Institute of Health Research INCLIVA, Valencia, Spain
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  • Belén Cortina,

    1. Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
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  • Salvador Lluch,

    1. Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
    2. Institute of Health Research INCLIVA, Valencia, Spain
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  • Pascual Medina

    Corresponding author
    1. Institute of Health Research INCLIVA, Valencia, Spain
    • Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
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  • Conflicts of interest: No conflicts of interest.

Correspondence

Dr Pascual Medina, Departamento de Fisiología, Facultad de Medicina y Odontología, Universidad de Valencia, Avenida Blasco Ibañez 15, 46010 Valencia, Spain. Email: pascual.medina@uv.es

Abstract

Background and Aim

Increased basal release of nitric oxide (NO) in the splanchnic circulation contributes to elevated plasma levels of NO observed in decompensated cirrhosis. We evaluated in rat mesenteric arteries whether the differences in basal release of NO, revealed by asymmetric dimethylarginine (ADMA)- and NG-nitro-L-arginine methyl ester (L-NAME)-induced contractions, were associated with changes in messenger RNA (mRNA) expression of endothelial NO synthase (eNOS) and dimethylarginine dimethylaminohydrolases (DDAHs).

Methods

Rat small mesenteric arteries from 14 Sham-control, from 14 with partial portal vein ligation (PPVL), and from 14 with bile duct excision (BDE)-induced cirrhosis were precontracted under isometric conditions with norepinephrine, and additional contractions were induced with ADMA and L-NAME. mRNA expression of eNOS, DDAH-1, and DDAH-2 in mesenteric arteries were evaluated by real-time polymerase chain reaction.

Results

ADMA and L-NAME caused concentration- and endothelium-dependent contractions. pD2 values to L-NAME were similar in all groups. In contrast, pD2 values to ADMA were similar in PPVL and BDE but were significantly lower than those of the L-NAME and the Sham groups. Relaxation to acetylcholine was not modified by ADMA or L-NAME but was abolished by charybdotoxin plus apamin. There was an increased mRNA expression of eNOS, DDAH-1, and DDAH-2 in mesenteric arteries from PPVL and BDE compared with the Sham group.

Conclusion

Basal release of NO is increased in mesenteric arteries of PPVL and BDE rats. The rise in expression of DDAHs indicates a higher degradation of ADMA. This would result in an increased generation of endothelial NO and mesenteric vasodilation.

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