Elsevier

Biochemical Pharmacology

Volume 25, Issue 17, 1 September 1976, Pages 1991-1993
Biochemical Pharmacology

Effects of alteration of hepatic microsomal enzyme activity on liver blood flow in the rat

https://doi.org/10.1016/0006-2952(76)90055-1Get rights and content

Abstract

The effects of pretreatment with ten daily intraperitoneal injections of phenobarbital (8 mg/100 g/day) 3,4-benzpyrene (1 mg/100 g/day and 3-methyl-cholanthrene (1 mg/100 g/day) and a single injection of SKF-525A (30 mg/kg) on liver blood flow in the rat were studied using radioactive microspheres. Of the hepatic enzyme-inducing agents only phenobarbital caused an increase in total liver blood flow, which averaged 33 per cent, and was associated with a similar increase in liver mass. The polycyclic hydrocarbons caused a small increase in liver mass of 11–15 per cent and no change in liver blood flow. All three agents induced drug-metabolizing enzymes, as judged by zoxazolamine paralysis time. SKF-525A produced no change in liver blood flow or liver mass. Liver blood flow/g of liver was unchanged in all groups. The increase in liver blood flow caused by phenobarbital was due entirely to an increase in flow to the splanchnic organs draining into the portal vein. These results imply that total hepatic blood flow is influenced by the mass of the liver and that the responsible, but as yet unknown, mechanism(s) involve the portal circulation. The different effect of phenobarbital and the polycyclic hydrocarbons on liver blood flow is only one of a number of distinctions between these inducing agents but may account for some of the differences observed in vivo especially with drugs whose clearance is dependent on liver blood flow.

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Supported in part by U.S. Public Health Service Grant GM 15431.

Burroughs Wellcome Scholar in Clinical Pharmacology.

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