Macrophage-dependent arachidonate metabolism in hydronephrosis.
Unilateral ureteral obstruction in rabbits leads to an influx of macrophages into the kidney, a proliferation of interstitial cells, and an increase in arachidonic acid metabolism. The role of the macrophage in the metabolic changes of hydronephrosis was investigated by using endotoxin and nitrogen mustard. The in vivo administration of endotoxin, a macrophage agonist, 1 hour before perfusion of the hydronephrotic kidney markedly enhanced (fourfold to tenfold) the peptide-stimulated arachidonic acid metabolism of the perfused kidney. Nitrogen mustard made animals leukopenic and prevented the influx of macrophages into the hydronephrotic kidney. The peptide-stimulated arachidonic acid metabolism of these kidneys was suppressed, and no enhancement was seen with in vivo endotoxin administration. The macrophage thus appears to be an essential determinant of the enhanced arachidonic acid metabolism seen in experimental hydronephrosis. An inhibitory effect of prostaglandin E2 on macrophage function in this model of renal inflammation was also demonstrated. Hydronephrotic animals were given aspirin during the period of unilateral ureteral obstruction to prevent in vivo prostaglandin E2 production. In the perfused hydronephrotic kidney, the peptide-stimulated arachidonic acid metabolism, which appears to be a marker of macrophage function in this model, was enhanced by aspirin treatment.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D015232:Dinoprostone; D004195:Disease Models, Animal; D004731:Endotoxins / Q000494:pharmacology; D006869:Hydronephrosis / Q000378:metabolism*; D007672:Kidney Cortex / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008466:Mechlorethamine / Q000494:pharmacology; D008861:Microsomes / Q000378:metabolism; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis; D013997:Time Factors
D001095:Arachidonic Acids; D004731:Endotoxins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D008466:Mechlorethamine; D013929:Thromboxane B2; D015232:Dinoprostone; D001241:Aspirin; D001920:Bradykinin