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Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats.
Liver Int. 2005 Jun; 25(3):647-56.LI

Abstract

BACKGROUND

Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. This study investigated the activity of nitric oxide synthase (NOS) in cirrhosis induced by bile duct-ligation (BDL) with NOS inhibitors.

METHOD

Three days after operation, rats were randomized to receive aminoguanidine (AG, 25 mg/kg/day) or L-N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) for 21 days.

RESULTS

Vascular NO production, which was increased in BDL cirrhotic rats, was reduced by 75% with AG but not L-NAME chronic administration. AG treatment attenuated liver damage, while L-NAME aggravated it. AG significantly suppressed inducible NOS (iNOS) expression in aorta of BDL rats at both mRNA and protein level, but much less efficient in reducing it in liver. In contrast, endothelial NOS (eNOS) expression was not markedly affected. Calcium-independent NOS activity, which was dramatically increased in aorta of BDL rats, was abolished by AG treatment. In liver, however, both calcium-dependent and -independent NOS activity were increased by AG treatment.

CONCLUSION

Chronic administration of AG could reduce systemic NO levels as well as suppress iNOS expression and activity in aorta of BDL rats. It also improved liver function, possibly because of its ability to increase hepatic NOS activity, and to correct the systemic hemodynamic disorders by decreasing vascular NO production.

Authors+Show Affiliations

Department of Paediatrics, Faculty of Medicine, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15910502

Citation

Wei, Chang-Li, et al. "Chronic Administration of Aminoguanidine Reduces Vascular Nitric Oxide Production and Attenuates Liver Damage in Bile Duct-ligated Rats." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 25, no. 3, 2005, pp. 647-56.
Wei CL, Hon WM, Lee KH, et al. Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats. Liver Int. 2005;25(3):647-56.
Wei, C. L., Hon, W. M., Lee, K. H., & Khoo, H. E. (2005). Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats. Liver International : Official Journal of the International Association for the Study of the Liver, 25(3), 647-56.
Wei CL, et al. Chronic Administration of Aminoguanidine Reduces Vascular Nitric Oxide Production and Attenuates Liver Damage in Bile Duct-ligated Rats. Liver Int. 2005;25(3):647-56. PubMed PMID: 15910502.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats. AU - Wei,Chang-Li, AU - Hon,Wei-Min, AU - Lee,Kang-Hoe, AU - Khoo,Hoon-Eng, PY - 2005/5/25/pubmed PY - 2005/10/7/medline PY - 2005/5/25/entrez SP - 647 EP - 56 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int VL - 25 IS - 3 N2 - BACKGROUND: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. This study investigated the activity of nitric oxide synthase (NOS) in cirrhosis induced by bile duct-ligation (BDL) with NOS inhibitors. METHOD: Three days after operation, rats were randomized to receive aminoguanidine (AG, 25 mg/kg/day) or L-N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) for 21 days. RESULTS: Vascular NO production, which was increased in BDL cirrhotic rats, was reduced by 75% with AG but not L-NAME chronic administration. AG treatment attenuated liver damage, while L-NAME aggravated it. AG significantly suppressed inducible NOS (iNOS) expression in aorta of BDL rats at both mRNA and protein level, but much less efficient in reducing it in liver. In contrast, endothelial NOS (eNOS) expression was not markedly affected. Calcium-independent NOS activity, which was dramatically increased in aorta of BDL rats, was abolished by AG treatment. In liver, however, both calcium-dependent and -independent NOS activity were increased by AG treatment. CONCLUSION: Chronic administration of AG could reduce systemic NO levels as well as suppress iNOS expression and activity in aorta of BDL rats. It also improved liver function, possibly because of its ability to increase hepatic NOS activity, and to correct the systemic hemodynamic disorders by decreasing vascular NO production. SN - 1478-3223 UR - https://www.unboundmedicine.com/medline/citation/15910502/Chronic_administration_of_aminoguanidine_reduces_vascular_nitric_oxide_production_and_attenuates_liver_damage_in_bile_duct_ligated_rats_ DB - PRIME DP - Unbound Medicine ER -