Hemodynamic effects of one week of carvedilol administration on cirrhotic rats.
BACKGROUND
Carvedilol is a nonselective beta-blocker with alpha(1)-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-PGF(1alpha) 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-PGF(1alpha) levels were not affected. In contrast, cirrhotic rats receiving carvedilol showed a significant decrease in serum nitrate/nitrite and 6-keto-PGF(1alpha) 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.
Lin
Han-Chieh
HC
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan.
Huang
Yi-Tsau
YT
Wei
Hung-Chi
HC
Yang
Ying-Ying
YY
Lee
Tzung-Yan
TY
Wang
Ying-Wen
YW
Hou
Ming-Chih
MC
Lee
Shou-Dong
SD
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D051545:Cyclooxygenase 1 / Q000097:blood / Q000235:genetics; D005500:Follow-Up Studies; D015870:Gene Expression; D006339:Heart Rate / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009566:Nitrates / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics; D009573:Nitrites / Q000097:blood; D016133:Polymerase Chain Reaction; D017082:Portal Pressure / Q000187:drug effects*; D011412:Propanolamines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D009566:Nitrates; D009573:Nitrites; D011412:Propanolamines; D012333:RNA, Messenger; D000077261:Carvedilol; D015121:6-Ketoprostaglandin F1 alpha; D052250:Nitric Oxide Synthase Type III; D051545:Cyclooxygenase 1