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Hemodynamic effects of one week of carvedilol administration on cirrhotic rats

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Abstract

Background

Carvedilol is a nonselective β-blocker with α1-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. The current study was undertaken to evaluate the possible mechanism of carvedilol on hemodynamics in cirrhotic rats with portal hypertension produced by common bile duct ligation.

Methods

Male Sprague-Dawley rats received either a sham operation or common bile duct ligation. Three weeks after surgery, both sham-operated and cirrhotic rats were randomly assigned to receive vehicle or carvedilol 5 mg · kg−1 · 12 h−1 by gastric gavage for 1 week. Hemodynamic measurements, serum biochemistry, serum nitrate/nitrite and 6-keto-PGF1α levels, and aortic mRNA expression of eNOS and COX-1 were performed on the eighth day after drug administration.

Results

Carvedilol treatment did not affect serum biochemistry in either sham-operated or cirrhotic rats. In sham-operated rats, administration of carvedilol significantly decreased the heart rate without affecting other hemodynamic values. In contrast, in cirrhotic rats, administration of carvedilol significantly decreased the cardiac index, portal pressure, heart rate, and portal territory blood flow, and it significantly increased systemic and portal territory vascular resistances. The hepatocollateral resistance was significantly decreased, but the hepatic arterial blood showed no significant changes. In sham-operated rats treated with carvedilol, serum nitrate/nitrite and 6-keto-PGF1α levels were not affected. In contrast, cirrhotic rats receiving carvedilol showed a significant decrease in serum nitrate/nitrite and 6-keto-PGF1α levels, associated with a decrease in aortic mRNA expression of eNOS and COX-1 compared with those receiving vehicle.

Conclusions

Carvedilol decreased portal pressure through a reduction of splanchnic blood flow associated with a decrease in hepatocollateral resistance. Additionally, administration of carvedilol decreased endothelial-related vasodilatory activities.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan

    Han-Chieh Lin, Ying-Ying Yang, Ying-Wen Wang, Ming-Chih Hou & Shou-Dong Lee

  2. Institute of Traditional Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Yi-Tsau Huang & Hung-Chi Wei

  3. Graduate Institute of Traditional Chinese Medicine, Chang Gung University, Taipei, Taiwan

    Tzung-Yan Lee

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  1. Han-Chieh Lin
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Lin, HC., Huang, YT., Wei, HC. et al. Hemodynamic effects of one week of carvedilol administration on cirrhotic rats. J Gastroenterol 41, 361–368 (2006). https://doi.org/10.1007/s00535-006-1782-5

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