Effect of vasodilators on hepatic microcirculation in cirrhosis: A study in the isolated perfused rat liver

• Published in: Hepatology (Baltimore, Md.) Md.), 1989-06, Vol.9 (6), p.820-823
• Main Authors: Marteau, Philippe, Ballet, François, Chazouillères, Olivier, Chrétien, Yves, Rey, Colette, Petit, Danielle, Poupon, Raoul
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiovascular system; In Vitro Techniques; Liver Circulation - drug effects; Liver Cirrhosis, Experimental - physiopathology; Male; Medical sciences; Microcirculation - drug effects; Norepinephrine - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Vascular Resistance - drug effects; Vasoconstriction - drug effects; Vasodilator Agents - pharmacology; Vasodilator agents. Cerebral vasodilators
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.1840090605

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 α1‐adrenergic antagonist (prazosin), a nonselective β‐adrenergic agonist (isoproterenol), an α2‐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.