Hemodynamic effects of nipradilol, a new beta-adrenergic antagonist combined with a nitroxy base, in rats with intra- or extra-hepatic portal hypertension.
It has been demonstrated that beta-adrenergic antagonists and nitrovasodilators reduce portal pressure in patients with portal hypertension. Thus, the hemodynamic effects of nipradilol, a new beta-adrenergic antagonist combined with a nitroxy base, was studied in conscious and unrestrained rats in two models of portal hypertension. The hemodynamic effects were compared to those obtained after propranolol administration. Both nipradilol (20 mg/kg) and propranolol (20 mg/kg) significantly decreased portal pressure in both groups of portal hypertensive rats. In cirrhotic rats, nipradilol decreased portal pressure (-24 +/- 2%) more than propranolol (-9 +/- 2%). Both nipradilol and propranolol significantly decreased portal tributary blood flow and cardiac index in both groups. Changes in portal tributary blood flow and cardiac index were not significantly different between nipradilol and propranolol. Propranolol, but not nipradilol significantly increased hepatocollateral resistance in cirrhotic rats but not in portal vein stenosed rats. Thus, the marked reduction of portal pressure after nipradilol administration depends in part on a limited increase in hepatocollateral resistance. Nipradilol significantly decreased mean arterial pressure, while propranolol did not change this value in either groups. In conclusion, nipradilol markedly decreased portal pressure in rats with portal hypertension. This beneficial effect suggests that nipradilol should be tested in the patients with portal hypertension.
Ohsuga
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Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Cailmail
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Lebrec
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D014677:Pharmaceutical Vehicles; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D014677:Pharmaceutical Vehicles; D011412:Propanolamines; D011433:Propranolol; C036089:nipradilol