Propranolol decreases portal pressure without changing portocollateral resistance in cirrhotic rats.
Propranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting. Two groups of rats with CCl4-induced cirrhosis were studied: the propranolol group (n = 8), which received a propranolol infusion of 2 mg per 15 min, and controls (n = 9), which received a placebo (saline) infusion. Hemodynamic measurements were done using radiolabeled microspheres. Propranolol-treated rats had significantly lower cardiac output (-31%) and heart rate (-26%) than controls (p less than 0.001). Hepatic artery flow was not modified by propranolol. Propranolol caused splanchnic vasoconstriction, manifested by increased splanchnic resistance (+57%) and by a significant fall in portal blood inflow (4.8 +/- 0.4 vs. 6.3 +/- 0.5 ml per min.100 gm in controls, p less than 0.05). In contrast with rats with prehepatic portal hypertension, propranolol did not increase portal resistance in cirrhotic rats [2.0 +/- 0.2 vs. 2.0 +/- 0.1 mmHg per ml per min.100 gm body weight (not significant)]. Hence, the fall in portal pressure (-19%) was expected from the decrease in portal inflow (-24%). These results suggest that increased portal resistance in rats with prehepatic portal hypertension may represent an intrinsic effect of propranolol on the portocollateral vessels, since beta-blockade does not modify portal vascular resistance in cirrhosis.
Pizcueta
M P
MP
Hepatic Hemodynamics Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
de Lacy
A M
AM
Kravetz
D
D
Bosch
J
J
Rodés
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002251:Carbon Tetrachloride; D002302:Cardiac Output / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014690:Venous Pressure / Q000187:drug effects
D011433:Propranolol; D002251:Carbon Tetrachloride