Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has recently been reported that the administration of ketanserin, a serotonin antagonist, was associated with a significant reduction in portal pressure both in portal hypertensive rats and cirrhotic patients. However, this beneficial effect on splanchnic hemodynamics was accompanied by a significant reduction in arterial pressure. Using conscious dogs, we investigated the effect of the chronic oral administration of a new specific antiserotonergic drug, ritanserin (10 mg per day for 5 days), on portal pressure and systemic hemodynamics. Eleven dogs with secondary biliary cirrhosis and portal hypertension due to chronic bile duct ligation were evaluated. One week prior to study, heparinized catheters were placed in the portal vein and brought subcutaneously to the dorsal cervical area. Measurements were made under baseline conditions, following ritanserin administration and 72 hr after the last dose. Ritanserin administration caused a significant reduction in portal pressure (from 17.3 +/- 3.1 mmHg to 13.6 +/- 4.5 mmHg; mean decrease: 23.1%; p less than 0.001). Maximal effects on portal pressure were reached on the fourth day. During the recovery period, hemodynamic parameters returned to baseline values. In six of the 11 cirrhotic dogs with successful chronic catheterization of the inferior vena cava and aorta, ritanserin administration did not cause significant changes in the mean arterial pressure, heart rate, cardiac output and peripheral vascular resistance. These data indicate that chronic implantation of venous and arterial catheters in dogs with secondary biliary cirrhosis is a useful experimental model for pharmacological studies of portal hypertension in conscious animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonin blockade in conscious, unrestrained cirrhotic dogs with portal hypertension. 249 51

This study investigated the short-term effects of ritanserin, a selective and specific S2-serotonergic antagonist, in an experimental model of cirrhosis and intrahepatic portal hypertension caused by long-term bile duct ligation and division and in normal control rats. The rats subjected to bile duct ligation were randomized under blind conditions into two groups to receive ritanserin (0.7 mg/kg body wt, intravenously; n = 10) or the same volume of placebo (isotonic saline solution; n = 10). We performed hemodynamic studies with radiolabeled microspheres 60 min after drug administration. Two groups of normal rats (n = 6) were studied after they received ritanserin or placebo. Ritanserin administration to rats subjected to bile duct ligation significantly reduced portal pressure (from 16.2 +/- 1.3 mm Hg to 12.3 +/- 0.7 mm Hg; mean decrease, 22% +/- 5%; p < 0.05). This reduction was associated with lower portal venous resistance (4.3 +/- 0.5 mm Hg.min.100gm/ml in the placebo group vs. 3.1 +/- 0.3 mm Hg.min.100 gm/ml in rats given ritanserin; mean decrease, 28%; p = 0.069), but we saw no changes in portal vein inflow (3.9 +/- 0.5 ml/min.100 gm vs. 4.4 +/- 0.4 ml/min.100 gm), mean arterial pressure (110 +/- 9 mm Hg vs. 102 +/- 9 mm Hg) and cardiac index (32.9 +/- 2.7 ml/min.100 gm vs. 40.5 +/- 6.7 ml/min.100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin. Ritanserin had no systemic or splanchnic effects in normal rats. Our results demonstrate that ritanserin infusion decreases portal pressure without any systemic hemodynamic change in rats with secondary biliary cirrhosis and portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in rats with long-term bile duct ligation. 834 68