Combined treatment of portal hypertension with ritanserin and propranolol in conscious and unrestrained cirrhotic rats.
We recently reported that ritanserin, a 5-hydroxytryptamine receptor antagonist, induced significant reduction of portal pressure in cirrhotic rats. In this study, we investigated the hemodynamic effects of a combination of propranolol and ritanserin in conscious and unrestrained cirrhotic rats. Heparinized catheters exiting from the neck were placed into the portal vein, inferior vena cava, aorta and left ventricle. Cardiac output and regional blood flows were measured with radiolabeled microspheres and the reference-sample method. Serial hemodynamic studies were performed 4 hr after rats awakened (basal), 1 hr after administration of ritanserin (0.63 mg/kg body wt, intravenously) and after intravenous propranolol infusion (0.33 mg/kg/min for 15 min) in nine cirrhotic rats. Similar measurements were obtained in a control group of eight cirrhotic rats treated with the solvents of ritanserin and propranolol. Ritanserin caused significant reduction of portal pressure (-19%). Portal-venous inflow and splanchnic arteriolar resistances remained unchanged, whereas portal-venous resistances were slightly but significantly lowered (-17%); and ritanserin had no effects on systemic hemodynamics. The addition of propranolol resulted in further reduction of portal pressure (-24%); the final reduction after combined therapy was -38%. Propranolol induced a marked decrease in cardiac output (-31%) and portal-venous inflow (-30%). It also caused a significant increase in splanchnic arteriolar resistance (+39%), but did not magnify the ritanserin-induced decrease of portal-venous resistance. The combined therapy did not modify the mean arterial pressure. Our results show that the effects of ritanserin on portal pressure--probably mediated by a reduction of intrahepatic and/or portocollateral resistances--can be potentiated by propranolol, which lowers the portal-venous inflow.
Pomier-Layrargues
G
G
Department of Medicine, Hôpital Saint-Luc, Montreal, Quebec, Canada.
Giroux
L
L
Rocheleau
B
B
Huet
P M
PM
D000818:Animals; D003243:Consciousness; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology; D008106:Liver Cirrhosis, Experimental / Q000150:complications*; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D016713:Ritanserin / Q000008:administration & dosage / Q000627:therapeutic use*
D016713:Ritanserin; D011433:Propranolol