Changes in liver blood flow during enzyme induction

Abstract

There is a difference between in vitro and in vivo measurements of the extent of enzyme induction. To explain this disparity we have measured changes in liver blood flow produced by three inducing agents—phenobarbitone (30 mg/kg for 4 days), antipyrine (30 mg/kg for 4 days) and 3,4-benzpyrene (40 mg/kg as a single injection). Flow was measured by a heat exchange method in conscious rats. Liver blood flow increased by 33–175 per cent above control values in rats treated with phenobarbitone and antipyrine but not in those given benzpyrene. The increase in liver blood flow was first seen at 24 hr and remained above control values for 2–8 days after treatment. In similarly operated rats phenobarbitone shortened the sleeping time to 5–10 per cent of control values with a similar time course to the changes in liver blood flow. The maximal velocity of N-demethylation of ethylmorphine increased from 4.9 to 17.2 nm/mg protein/min, the maximal increase occurring 2–3 days after starting phenobarbitone. It is suggested that the increase in liver blood flow may be due to increases in liver weight and enzyme activity.