Effect of thioridazine and chlorpromazine on rat liver hemodynamics

¹ Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana

Evidence is presented which indicates that two phenothiazine derivatives—thiroidazine and chlorpromazine— increase hepatic vascular resistance in isolated perfused rat livers. These substances produce the following: a) a decrease in perfusate flow through the organ, b) an increase in portal pressure and c) a decrease in organ weight. These effects were demonstrated with doses as low as 4 mg but were quantitatively more pronounced and of longer duration with higher doses. Tachyphylaxis did not occur. The effects could be blocked with sodium nitrite. Both phenothiazines were found to produce liver ischemia in anesthetized, laparotomized rats. Thioridazine was found to raise portal pressure in anesthetized, laparotomized cats in spite of a marked decrease in mean arterial pressure.