Ritanserin decreases portal pressure in conscious and unrestrained cirrhotic rats.
We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and systemic hemodynamic effects of ritanserin (0.63 mg/kg body wt i.v., a dose known to completely inhibit binding of 5-hydroxytryptamine to its receptors), in conscious and unrestrained cirrhotic rats (n = 13). Heparinized catheters were placed into the portal vein, inferior vena cava, aorta, and left ventricle with exit from the neck. Hemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabeled microspheres and the reference sample method. Sixty minutes after administration, ritanserin caused a significant reduction of portal pressure (-17%) with minimal changes in portal venous inflow (+3%). Portal vascular resistance decreased significantly (-23%), whereas splanchnic arteriolar resistance was similar before and after ritanserin. A significant increase in mean arterial pressure (+5%) and cardiac output (+22%) was observed. Our results suggest that ritanserin lowers portal pressure through a mechanism separate from portal venous inflow. This effect could be due to changes in intrahepatic or on portocollateral resistances, or both. These findings support the potential use of this new agent in the treatment of portal hypertension.
Mastai
R
R
Hôpital Saint-Luc, André-Viallet Clinical Research Center, Montreal, Quebec, Canada.
Giroux
L
L
Semret
M
M
Huet
P M
PM
D000818:Animals; D003243:Consciousness; D003864:Depression, Chemical; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000188:drug therapy*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013152:Splanchnic Circulation / Q000187:drug effects
D010880:Piperidines; D012702:Serotonin Antagonists; D016713:Ritanserin