Role of Inflammatory Cells in Metabolic and Cellular Alterations Underlying the Exaggerated Renal Prostaglandin and Thromboxane Synthesis in Ureter Obstruction

  • Philip Needleman
Part of the New Horizons in Therapeutics book series (NHTH)


Perfused normal rabbit kidney releases modest amounts of prostaglandin (PG) E2 in response to vasoactive peptides (bradykinin and angiotensin II) (Needleman et al., 1973). In microsomes prepared from the normal kidney, the medulla is the primary site of arachidonic acid metabolism; much less PG produetion occurs in the cortex (Larsson and Anggard, 1974). Unilateral Ureter obstruction (hydronephrosis) for several days results in a marked facilitation of (1) PGE2 release from an isolated perfused kidney (Nishikawa et al, 1977), (2) cortical microsomal arachidonate metabolism (Morrison et al., 1977; Needleman et al., 1979), and (3) cortical slice PG release (Currie et al, 1981). In addition, the perfused hydronephrotic kidney (HNK) has been demonstrated to release thromboxane A2 (TxA2). The thromboxane synthetase activity is clearly evident in HNK cortical microsomes, whereas this enzyme is not detectable in normal or contralateral unobstrueted rabbit kidneys (CLK) (Morrison et al, 1977, 1978). Measurement of prostaglandins by radioimmunoassay demonstrated that PGE2 , 6-keto-PGF, and TxB2 levels are increased in the venous effluent of the hydronephrotic kidney in both the basal and hormone-stimulated states (e.g., bradykinin and angiotensin) (Reingold et al, 1981). The release of these substances could be blocked with indomethacin treatment.


Unilateral Ureter Obstruction Ureteral Obstruction Ureter Obstruction Rabbit Kidney PGE2 Release 
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Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Philip Needleman
    • 1
  1. 1.Department of PharmacologyWashington University School of MedicineSt. LouisUSA

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