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

Authors

  • Philippe Marteau,

    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
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    • P. Marteau held a fellowship from the Fondation pour la Recherche Médicale.

  • François Ballet M.D.,

    Corresponding author
    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
    • Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, F-75012 Paris, France
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  • Olivier Chazouillères,

    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
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  • Yves Chrétien,

    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
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  • Colette Rey,

    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
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  • Danielle Petit,

    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
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  • Raoul Poupon

    1. Equipe de Physiologie et de Pharmacologie Hépatique, INSERM U.181, Hǒpital Saint-Antoine, Paris, France
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Abstract

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.

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