EVIDENCE FOR 2 DISTINCT AND FUNCTIONALLY IMPORTANT SITES OF ENHANCED THROMBOXANE PRODUCTION AFTER BILATERAL URETERAL OBSTRUCTION IN THE RAT

1. After bilateral ureteral obstruction there is an enhanced production of thromboxane A2 by the kidney which contributes to a decline in renal function. An acute interstitial macrophage infiltrate also occurs. 2. The relative contribution of infiltrating cells and intrinsic renal cells to the enhanced production of thromboxane A2 by the hydronephrotic kidney were determined. The effects of both irradiation and subsequent administration of the thromboxane synthesis inhibitor OKY-046 on both thromboxane B2 excretion and renal function were examined in rats with 24 h bilateral ureteral obstruction. 3. Irradiation effectively prevented the leucocyte infiltrate after bilateral ureteral obstruction (1.2 +/- 0.8 x 10(5) versus 27.1 +/- 0.1 x 10(5) cells/g of cortex, n = 4 in each group), resulted in a significantly higher inulin clearance (2.78 +/- 0.27 versus 1.49 +/- 0.17 ml min-1 kg-1 body weight, n = 7 and n = 8, respectively, P < 0.001) and reduced thromboxane B2 excretion to 39% of non-irradiated values. Subsequent administration of OKY-046 to previously irradiated animals further reduced thromboxane B2 excretion to 20% of the value in non-irradiated rats with bilateral obstruction and further increased inulin clearance to 3.34 +/- 0.26 ml min-1 kg-1 body weight. 4. Glomerular macrophage numbers were decreased after bilateral ureteral obstruction (in contrast to the interstitium). However, glomeruli isolated from rats with 24 h bilateral ureteral obstruction exhibited enhanced production of thromboxane B2 compared with sham-operated control rats (855.6 +/- 31.1 versus 392.2 +/- 25.5 pg 60 min-1 mg-1 of protein, P < 0.001). 5. These data suggest that the increased renal production of thromboxane A2 after bilateral ureteral obstruction results from both renal infiltration by metabolically active macrophages and enhanced prostanoid production by the glomeruli. Both sources of thromboxane A2 contribute to altered renal function after bilateral ureteral obstruction.