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.