Enzyme activity in obstructive uropathy: Basis for salt wastage and the acidification defect

Enzyme activity in obstructive uropathy: Basis for salt wastage and the acidification defect. Unilateral ureteral obstruction results in marked changes in renal function throughout the nephron, including impaired acid and potassium secretion and salt wastage. The nephron site believed responsible for the acidification defect is the collecting duct. It has been presumed, although not demonstrated, that the cellular mechanism for the acidification defect is both a decrease in transepithelial voltage and a decrease in activity of the proton pump located at the luminal membrane. The mechanism for the abnormalities in sodium handling are thought due to alterations in Na-K ATPase activity. Our laboratory has recently mapped the profile of the N-ethylmaleimide (NEM)-sensitive ATPase and Na-K ATPase in microdissected rat nephron, documenting their presence throughout much of the nephron. In animals with acute unilateral ureteral obstruction for 18 to 24 hours, we measured NEM-sensitive ATPase and Na-K ATPase activities in several nephron sites. In all nephron segments Na-K ATPase activity was markedly decreased. In the medullary collecting duct, NEM-sensitive ATPase activity was also markedly reduced in animals with acute ureteral obstruction; in the cortical collecting duct, activity fell significantly, but to a lesser degree than was observed in the medullary collecting duct. NEM-sensitive ATPase activity was unchanged from control in the proximal convoluted tubule and in the medullary thick ascending limb; in the cortical thick ascending limb enzyme activity increased. These results demonstrate a change in both Na-K ATPase and NEM-sensitive ATPase activities as a direct consequence of a defect known to result in salt wastage and an acidification defect in humans and animals. Our findings show that while NEM-sensitive ATPase activity is abnormal in cortical collecting duct, the medullary collecting duct is the most severely affected.