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Effect of vasodilators on hepatic microcirculation in cirrhosis: A study in the isolated perfused rat liver
Author(s) -
Marteau Philippe,
Ballet François,
Chazouillères Olivier,
Chrétien Yves,
Rey Colette,
Petit Danielle,
Poupon Raoul
Publication year - 1989
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840090605
Subject(s) - prazosin , propranolol , verapamil , vasodilation , diazoxide , papaverine , phentolamine , medicine , nifedipine , pentoxifylline , endocrinology , diltiazem , vasoconstriction , pharmacology , antagonist , calcium , receptor , insulin
We studied the effects of a series of vasodilators on intrahepatic vascular resistance of isolated perfused cirrhotic rat livers in basal conditions and during norepinephrine‐induced vasoconstriction. Cirrhosis was induced by repeated intraperitoneal injections of carbon tetrachloride. The vasodilators were a nonselective β‐adrenergic antagonist (propranolol), an α 1 ‐adrenergic antagonist (prazosin), a nonselective β‐adrenergic agonist (isoproterenol), an α 2 ‐agonist (clonidine), nitrovasodilators (nitroglycerin and nitroprusside), calcium channel blockers (verapamil, diltiazem, nifedipine), papaverine, diazoxide and pentoxifylline. In basal conditions, isoproterenol, nitroglycerin, papaverine, pentoxifylline and nitroprusside demonstrated significant vasodilatory activity. However, the response was weak and isoproterenol was the only drug active in the therapeutic range of concentrations. Propranolol, prazosin, verapamil, diltiazem, nifedipine and diazoxide were ineffective. Prazosin, papaverine and pentoxifylline reduced norepinephrine‐induced vasoconstriction, whereas isoproterenol, clonidine and propranolol were ineffective. We conclude that several vasodilators can reduce resistance in the cirrhotic rat liver, but their potency is low and few are effective at therapeutic concentrations. Furthermore, their activity may be blunted when resistance is increased by norepinephrine.