Endotoxin induces chronic prostaglandin and thromboxane synthesis from ureter-obstructed kidneys: role of inflammatory cells.

A bolus injection of a very low dose (100 ng) of endotoxin into an isolated perfused hydronephrotic (3 day unilateral ureter obstructed) kidney resulted in the appearance of substances in the venous effluent, which caused a biphasic chronic contraction of intestinal and vascular smooth muscle bioassay strips. Indomethacin pretreatment blocked the effect. The contralateral (unobstructed) rabbit kidney, postobstructed hydronephrotic rabbit kidney (i.e., release of ureter obstruction for 3-10 days) and the hydronephrotic cat kidney did not respond to endotoxin. Histological examination demonstrated that the hydronephrotic rabbit kidney contains mononuclear cells, whereas the unobstructed contralateral rabbit kidney as well as the postobstructed rabbit hydronephrotic kidney and the hydronephrotic cat kidney have considerably fewer mononuclear cells. The responsiveness of the hydronephrotic rabbit kidney to endotoxin is dependent on ex vivo perfusion time and is suppressed by inhibition of protein synthesis with cycloheximide. These data suggest that ureter obstruction in the rabbit stimulates the infiltration of macrophages which are sensitive to endotoxin and which participate in the exaggerated prostaglandin production.