Regional expression of inducible nitric oxide synthase in the kidney in dogs with unilateral ureteral obstruction

Purpose: In the early stage of unilateral ureteral obstruction total renal blood flow increases but medullary blood flow decreases, exacerbating medul lary tissue hypoxia. We examined the expression of inducible nitric oxide s ynthase, a product of a hypoxia sensitive gene, in the cortex and medulla i n dogs with unilateral ureteral obstruction for 21 hours. Materials and Methods: Hemodynamic and clearance experiments were performed after release of ureteral obstruction in 6 dogs with unilateral ureteral o bstruction, followed by Western blot analysis of nitric oxide synthase and immunohistochemistry. Results: Ureteral obstruction raised mean ureteral pressure plus or minus s tandard error to 35.0 +/- 7.2 mm. Hg. In dogs with unilateral ureteral obst ruction 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 unilatera l 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 c ontralateral unobstructed kidney (p <0.01). Western blot analysis showed th at mean nitric oxide synthase/beta -actin in the cortex of the obstructed k idney was 0.04 +/- 0.01 densitometry units, lower than 0.11 +/- 0.02 densit ometry units in the unobstructed contralateral kidney (p <0.05). In contras t, 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). Immunohistochemis try revealed that the increased expression of nitric oxide synthase protein was localized to the endothelium of the vasa recta. Conclusions: 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 unilate ral ureteral obstruction, possibly contributing to medullary hyperemia afte r unilateral ureteral obstruction release.