Cocaine-induced changes in perfusion pressure and bile flow in perfused rat livers.
Cocaine produces hepatotoxicity. To study the acute effect of cocaine on the liver, we used the isolated, single-pass perfused rat liver. When perfusion pressure was measured in a constant flow system, a 15-min infusion of cocaine (1.47 mM) increased perfusion pressure (136 +/- 15%), decreased bile flow (61 +/- 5%), and decreased oxygen uptake (82 +/- 5%). The vasoconstriction was concentration-dependent and reversible. The pressure increase elicited by cocaine was not inhibited by the alpha-receptor antagonists phentolamine, prazosin, or yohimbine. These antagonists did inhibit phenylephrine-induced increases in perfusion pressure. Neither serotonin at concentrations up to 1 mM nor lidocaine or procaine in concentrations equimolar to cocaine increased the perfusion pressure. Indomethacin (5 microM), SKF-525A, and chloramphenicol also failed to block vasoconstriction induced by cocaine. High concentrations of cocaine were cholestatic, while concentrations lower than 0.6 mM were choleretic. These results indicate that cocaine-induced vasoconstriction in the liver is not mediated by alpha-receptor activation or prostaglandins and does not require metabolic activation of cocaine. The acute effects of cocaine in the perfused liver are vascular (vasoconstriction) and functional (alteration in bile formation).
Garhart
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Department of Pharmacology, Tufts University School of Medicine, Boston, MA 02111.
Anwer
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Shuster
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D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D000779:Anesthetics, Local; D015016:Yohimbine; D010208:Papaverine; D003042:Cocaine; D007213:Indomethacin; D010646:Phentolamine