Roles for thromboxane A2 and leukotrienes in endotoxin-induced acute renal failure.
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)
D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D015232:Dinoprostone; D004731:Endotoxins / Q000633:toxicity*; D011464:Epoprostenol / Q000502:physiology; D004926:Escherichia coli; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011458:Prostaglandins E / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000502:physiology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects
D002867:Chromones; D004731:Endotoxins; D007093:Imidazoles; D011458:Prostaglandins E; D013189:SRS-A; C029166:dazoxiben; D013928:Thromboxane A2; C006312:FPL 55712; D011464:Epoprostenol; D015232:Dinoprostone