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Lack of detrimental effects of nitric oxide inhibition in bile duct-ligated rats with hepatic encephalopathy

Authors


  • Division of Gastroenterology, Department of Medicine (C.-Y. Chan, T.-F. Wang, R.-H. Lu, F.-Y. Lee, F.-Y. Chang, C.-J. Chu, Y.-C. Chen, C.-C. Chan, H.-C. Huang, S.-D. Lee) and Department of Medical Research and Education (C.-Y. Chan), Taipei Veterans General Hospital; Armed Forces Sungshan Hospital (T.-F. Wang); National Yang-Ming University School of Medicine (C.-Y. Chan, S.-W. Huang, F.-Y. Lee, F.-Y. Chang, C.-J. Chu, C.-C. Chan, H.-C. Huang, S.-D. Lee), Taipei, Taiwan.

Fa-Yauh Lee, MD, FACG, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No 201, Sec 2, Shih-pai Road, Taiwan, 11217. Tel.: 886–2–28757308; fax: 886–2–28739318; e-mail: fylee@vghtpe.gov.tw

Abstract

Background  The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Vasodilatation induced by nitric oxide (NO) may be involved in the development of HE. There is no comprehensive data concerning the effects of NO inhibition on HE in chronic liver disease.

Methods  Male Sprague-Dawley rats weighing 240–270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Counts of movements were compared between BDL rats and rats receiving a sham operation. In another series of experiments, BDL rats received either Nω-nitro-L-arginine methyl ester (L-NAME, 25 mg kg−1 day−1 in tap water) or tap water (control) from the 36th to 42nd days after BDL. Besides motor activities, plasma levels of tumour necrosis factor (TNF)-α and nitrate/nitrite, liver biochemistry tests and haemodynamics were determined after treatment.

Results  Compared with the sham-operated rats, the total, ambulatory and vertical movements were significantly decreased in the BDL rats (P ≤ 0·001). The L-NAME group had a significantly higher mean arterial pressure than that of the control group (119·0 ± 2·5 mmHg vs. 97·3 ± 2·8 mmHg, P = 0·002). However, the counts of motor activities, plasma levels of TNF-α and nitrate/nitrite, and serum biochemistry tests were not significantly different between the L-NAME and control groups.

Conclusions  Bile duct ligation may induce HE evidenced by a decrease in motor activities. However, chronic L-NAME administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.

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