Roles for thromboxane A2 and leukotrienes in endotoxin-induced acute renal failure

Kidney Int. 1986 Oct;30(4):474-80. doi: 10.1038/ki.1986.210.

Abstract

Bolus i.v. administration of 100 micrograms/kg of E. Coli lipopolysaccharide endotoxin (LPS) to adult male Munich-Wistar rats (N = 18) resulted in a progressive fall in RBF and GFR from 6.9 +/- 0.2 SE and 1.1 +/- 0.05 ml/min to minimal values at 50 minutes of 3.8 +/- 0.4 and 0.32 +/- 0.08 (P less than 0.05), respectively, without a fall in mean arterial pressure. At 50 minutes, renal cortical generation rates of PGE2 (1075 +/- 108 pg/mg tissue), 6 keto PGF1 alpha (221 +/- 41 pg/mg), and TxB2 (106 +/- 12 pg/mg) were significantly higher than those of vehicle-treated control rats (N = 10, PGE2 = 466 +/- 107, 6 keto PGF1 alpha = 94 +/- 3, and TxB2 = 35 +/- 3 pg/mg), and morphologic examination revealed normal histology with notable absence of leukocytes and platelets. Pretreatment of a third group of nine rats with TxA2 synthetase inhibitor UK-37.248 (dazoxiben, 10 mg/kg) selectively abolished the LPS-induced rise in TxB2 (29 +/- 3 pg/mg), but not PGE2 (837 +/- 62 pg/mg) or 6 keto PGF1 alpha (179 +/- 5 pg/mg), prevented the fall in RBF at 50 minutes (6.3 +/- 0.4 ml/min), and allowed for significant preservation of GFR (0.67 +/- 0.08 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / physiopathology
  • Animals
  • Chromones / pharmacology
  • Dinoprostone
  • Endotoxins / toxicity*
  • Epoprostenol / physiology
  • Escherichia coli*
  • Glomerular Filtration Rate / drug effects
  • Imidazoles / pharmacology
  • Kidney / drug effects
  • Kidney / physiopathology
  • Male
  • Prostaglandins E / physiology
  • Rats
  • Rats, Inbred Strains
  • SRS-A / antagonists & inhibitors
  • SRS-A / physiology*
  • Thromboxane A2 / antagonists & inhibitors
  • Thromboxane A2 / physiology*
  • Vascular Resistance / drug effects

Substances

  • Chromones
  • Endotoxins
  • Imidazoles
  • Prostaglandins E
  • SRS-A
  • dazoxiben
  • Thromboxane A2
  • FPL 55712
  • Epoprostenol
  • Dinoprostone