Effect of 16,16-dimethyl prostaglandin E2 on oxygen uptake and microcirculation in the perfused rat liver

Authors

  • Haruya Meren,

    1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514
    2. Diabetes and Gastrointestinal Research, The Upjohn Company, Kalamazoo, Michigan 49001
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  • France Varin,

    1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514
    2. Diabetes and Gastrointestinal Research, The Upjohn Company, Kalamazoo, Michigan 49001
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  • Mary Ruwart,

    1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514
    2. Diabetes and Gastrointestinal Research, The Upjohn Company, Kalamazoo, Michigan 49001
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  • Ronald G. Thurman Ph.D.

    Corresponding author
    1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514
    2. Diabetes and Gastrointestinal Research, The Upjohn Company, Kalamazoo, Michigan 49001
    • University of North Carolina at Chapel Hill, School of Medicine, Department of Pharmacology, Chapel Hill, North Carolina 27514
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Abstract

Previous work demonstrated that collagen deposition in the liver of rats fed a nutritionally deficient diet for 3 to 4 months was diminished markedly by 16,16-dimethyl prostaglandin E2 treatment. In this study, rats were fed a high-fat diet or a high-fat diet deficient in lipotropes for 2 to 4 weeks prior to liver perfusion. Rates of O2 uptake by the liver were not changed by dietary manipulation. Infusion of 16,16-dimethyl prostaglandin E2 (10 μM), however, decreased O2 uptake by the whole organ by 20 to 40% in both groups. O2 tension was measured at the liver surface with a miniature O2 electrode placed alternatively on periportal and pericentral regions of the liver lobule. Mean O2 tensions in both periportal and pericentral regions were reduced 2- to 3-fold during the infusion of 16,16-dimethyl prostaglandin E2 suggesting an action on the microcirculation. This hypothesis was supported by the observation that fluorescein isothiocyanate-dextran fluorescence detected from the liver surface as well as hepatic vascular volume determined by dye dilution techniques were decreased 30 to 50% by 16,16-dimethyl prostaglandin E2. In addition, 16,16-dimethyl prostaglandin E2 increased portal pressure by about 10 mm Hg in a reversible manner. Thus, it is concluded that pharmacological levels of 16,16-dimethyl prostaglandin E2 affects the microcirculation dramatically in the isolated perfused liver.

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