Localization of exaggerated prostaglandin synthesis associated with renal damage.
Regional localization of the exaggerated prostaglandin E2 (PGE2) synthesis caused by hydronephrosis was studied in unilateral ureteral ligated rabbits. The renal distribution of PGE2 production was compared in the hydronephrotic and contralateral kidneys. Basal and bradykinin-stimulated PGE2 synthesis were increased in cortical and medullary slices of the hydronephrotic kidneys. Contralateral (control) cortical slices produced very low levels of PGE2 and were insensitive to stimulation by bradykinin (BK). The hydronephrotic cortex produced 10 times more PGE2 than the contralateral cortex and responded to BK stimulation with increased PGE2 synthesis. Cortical slices from the hydronephrotic kidney exhibited a time-dependent increase in PGE2 release, presumably as a result of new protein synthesis. The division of the hydronephrotic cortex into outer and inner regions revealed that the inner cortex produced more PGE2 than the outer cortex. A similar division of the hydronephrotic medulla showed that the inner medulla produced slightly greater amounts of PGE2 than the outer medulla. The present study demonstrates that hydronephrosis causes increases in prostaglandin synthesis throughout the kidney. We suggest from these results and other studies that a possible explanation for this finding is the involvement of the collecting duct system in this response. The gradient of PGE2 production detected in the cortex may have a very significant role in the control of renal hemodynamics and could provide an explanation for the large decrease in blood flow to the inner cortex caused by indomethacin treatment.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D015237:Dinoprost; D006869:Hydronephrosis / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D011460:Prostaglandins F / Q000096:biosynthesis*; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution
D011460:Prostaglandins F; D003513:Cycloheximide; D015237:Dinoprost; D001241:Aspirin; D001920:Bradykinin