REGIONAL EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE IN THE KIDNEY IN DOGS WITH UNILATERAL URETERAL OBSTRUCTION

Abstract

In the early stage of unilateral ureteral obstruction total renal blood flow increases but medullary blood flow decreases, exacerbating medullary tissue hypoxia. We examined the expression of inducible nitric oxide synthase, a product of a hypoxia sensitive gene, in the cortex and medulla in dogs with unilateral ureteral obstruction for 21 hours. Hemodynamic and clearance experiments were performed after release of ureteral obstruction in 6 dogs with unilateral ureteral obstruction, followed by Western blot analysis of nitric oxide synthase and immunohistochemistry. Ureteral obstruction raised mean ureteral pressure plus or minus standard error to 35.0 +/- 7.2 mm. Hg. In dogs with unilateral ureteral obstruction mean renal blood flow was 116 +/- 10 ml. per minute, lower than the 213 +/- 22 ml. per minute in sham operated dogs (p <0.01). After unilateral ureteral obstruction release the mean glomerular filtration rate was 9.5 +/- 2.1 ml. per minute, lower than the 27.3 +/- 1.8 ml. per minute in the contralateral unobstructed kidney (p <0.01). Western blot analysis showed that mean nitric oxide synthase/beta-actin in the cortex of the obstructed kidney was 0.04 +/- 0.01 densitometry units, lower than 0.11 +/- 0.02 densitometry units in the unobstructed contralateral kidney (p <0.05). In contrast, mean nitric oxide synthase/beta-actin in the medulla of the obstructed kidney was 1.29 +/- 0.33 densitometry units, greater than the 0.34 +/- 0.03 densitometry units in the unobstructed kidney (p <0.05). Immunohistochemistry revealed that the increased expression of nitric oxide synthase protein was localized to the endothelium of the vasa recta. Unilateral ureteral obstruction enhances nitric oxide synthase expression in the medulla but not in the cortex. This increased expression in the medulla may be the result of increased medullary hypoxia in unilateral ureteral obstruction, possibly contributing to medullary hyperemia after unilateral ureteral obstruction release.