Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in portal hypertensive rats.
Serotonergic mechanisms have recently been implicated in the pathogenesis of portal hypertension; this suggests that blockade of serotonin S2 receptors may be a new approach for the pharmacological therapy of portal hypertension. This study was aimed at investigating the effects of ritanserin, a selective S2-serotonergic antagonist, in portal-hypertensive rats whose condition was due to partial portal vein ligation. The animals were randomized under double-blind conditions into two groups: the first received ritanserin (0.7 mg/kg body wt, intravenously), and the second received the same volume of placebo (isotonic saline solution). The hemodynamic studies were performed using radiolabeled microspheres 60 min after drug administration. Ritanserin administration significantly reduced portal pressure (from 11.8 +/- 0.8 mm Hg to 9.4 +/- 0.6 mm Hg; p less than 0.05). This was associated with lower portocollateral resistance (1.8 +/- 0.2 mm Hg/ml/min 100 gm in the ritanserin group vs. 2.3 +/- 0.2 mm Hg/ml/min 100 gm in rats receiving placebo; not significant), but we saw no changes in portal-vein inflow (5.5 +/- 0.7 ml/min 100 gm vs. 5.4 +/- 0.5 ml/min 100 gm), mean arterial pressure (95.9 +/- 3.5 mm Hg vs. 94.0 +/- 4.0 mm Hg) and cardiac index (31.9 +/- 3.5 ml/min 100 gm vs. 28.5 +/- 2.6 ml/min 100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin. In summary, our results demonstrate that ritanserin infusion decreases portal pressure without causing systemic hemodynamic changes. This effect is probably due to a decrease in portocollateral resistance in portal-hypertensive rats. These results provide further for a role of serotonin in the pathogenesis of portal hypertension.
Nevens
F
F
Hepatic Hemodynamics Laboratory, Hospital Clínic i Provincial, Barcelona, Spain.
Pizcueta
M P
MP
Fernández
M
M
Bosch
J
J
Rodés
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000503:physiopathology*; D008297:Male; D011168:Portal System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D016713:Ritanserin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*
D012702:Serotonin Antagonists; D016713:Ritanserin