Regional Expression of Cyclooxygenase Isoforms in the Rat Kidney in Complete Unilateral Ureteral Obstruction

Abstract

The cyclooxygenase (COX) pathway is activated in unilateral ureteral obstruction (UUO), contributing to renal hemodynamic alterations in different regions of the kidney. After the release of 24-hour UUO cortical vasoconstriction occurs but medullary hyperemia is seen. We examined the expression of the 2 COX isoforms COX-1 and COX-2 in different regions of the kidney in rats subjected to UUO. Clearance experiments were performed after ureteral obstruction release in rats with 24-hour UUO or sham operated rats. COX-1 and COX-2 expression in the cortex and medulla were examined by Western blot analysis and immunohistochemistry. After UUO release the glomerular filtration rate and renal plasma flow were markedly lower in post-obstructed kidneys than in contralateral kidneys or in kidneys in sham operated rats (p <0.001). Western blot analysis showed that COX-2/beta-actin in the cortex of the obstructed kidney was 0.28 +/- 0.02 densitometry units, significantly lower than 0.67 +/- 0.12 densitometry units in the contralateral unobstructed kidney. In contrast, COX-2/beta-actin in the outer and inner medullae of the obstructed kidney was 7.85 +/- 1.09 and 2.51 +/- 0.14 densitometry units, significantly greater than 3.03 +/- 0.22 and 0.66 +/- 0.14 densitometry units, respectively, in the contralateral unobstructed kidney. The expression of COX-1/beta-actin in the obstructed kidney was similar to that in the contralateral unobstructed kidney in the cortex and medulla. Renal COX-2 expression is markedly altered in UUO. Decreased cortical expression of COX-2 and markedly increased expression in the medulla may contribute to disparate regional hemodynamic alterations in UUO.