Immunohistochemical distribution of renal prostaglandin endoperoxide synthase and prostacyclin synthase: Diminished endoperoxide synthase in the hepatorenal syndrome

Authors

  • Sugantha Govindarajan,

    1. University of Southern California Liver Unit, Rancho Los Amigos Hospital, Downey, California 90024
    2. Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824
    3. Departments of Pathology, Surgery and Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
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  • Cynthia C. Nast,

    1. University of Southern California Liver Unit, Rancho Los Amigos Hospital, Downey, California 90024
    2. Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824
    3. Departments of Pathology, Surgery and Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
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  • William L. Smith,

    1. University of Southern California Liver Unit, Rancho Los Amigos Hospital, Downey, California 90024
    2. Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824
    3. Departments of Pathology, Surgery and Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
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  • Martin A. Koyle,

    1. University of Southern California Liver Unit, Rancho Los Amigos Hospital, Downey, California 90024
    2. Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824
    3. Departments of Pathology, Surgery and Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
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  • George Daskalopoulos,

    1. University of Southern California Liver Unit, Rancho Los Amigos Hospital, Downey, California 90024
    2. Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824
    3. Departments of Pathology, Surgery and Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
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  • Robert D. Zipser M.D.

    Corresponding author
    1. University of Southern California Liver Unit, Rancho Los Amigos Hospital, Downey, California 90024
    2. Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824
    3. Departments of Pathology, Surgery and Medicine, Harbor-UCLA Medical Center, Torrance, California 90509
    • Division of Gastroenterology, C-1 Trailer, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, California 90509
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Abstract

To evaluate possible causes of the diminished prostaglandin production in advanced hepatorenal syndrome, prostaglandin endoperoxide synthase and prostacyclin synthase were localized and semiquantitated by immunofluorescence in postmortem, biopsy and nephrectomy renal tissues. In normal kidneys, antiprostacyclin synthase serum caused intense staining in peritubular capillaries, in the adjacent renal interstitial cells and in glomerular mesangial regions. Antiprostaglandin endoperoxide synthase serum caused staining of collecting duct epithelial cells, cells of the thin ascending limb and possibly glomerular mesangial cells. Prostacyclin synthase-positive staining was graded 5+ (scale of 0+ to 5+) in all kidney samples. Medullary collecting tubule prostaglandin endoperoxide synthase-positive staining was graded 4+ or 5+ in kidney samples from patients with acute tubular necrosis or acute tubulointerstitial nephritis and from patients with liver failure without the hepatorenal syndrome. However, prostaglandin endoperoxide synthase-positive staining was markedly diminished or absent (average 1+) in patients with the hepatorenal syndrome. These data suggest that loss of the medullary prostaglandin endoperoxide synthase is the cause of diminished urinary prostaglandin E2 excretion in the hepatorenal syndrome.

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