Oxidant stress leads to impaired regulation of renal cortical XXXX consumption by @entity842 in the aging kidney.

@entity11933 @entity12824 @entity26 @entity1110 @entity842 @entity3591 @entity1812 @entity35 @entity224
Structural and functional changes occur in the kidney with aging. Previous studies have suggested that loss of @entity842 production contributes to these changes. The authors therefore explored regulation of renal cortical @entity26 consumption, a @entity842 mediated effect, in tissue from Fischer 344 @entity35 at different ages (4, 13, and 23 mo) to characterize changes in renal @entity842 production with age. @entity1812 , enalaprilat, and @entity3591 significantly suppressed cortical @entity26 consumption in 4-mo-old @entity35 ( @entity1812 : -2.5 +/- 0.9% to -21 +/- 1.5%; enalaprilat: -0.7 +/- 0.5% to -26 +/- 1.2%; @entity3591 : -1.3 +/- 0.9% to -18 +/- 1.2%; P < 0.05). Similar results were obtained in 13-mo-old animals. However, in 23-mo-old animals, the responses to @entity1812 and enalaprilat were attenuated ( @entity1812 : 0 +/- 0% to -13 +/- 0.9%; enalaprilat: -0.3 +/- 0.3% to -17 +/- 2.1%; P < 0.05), whereas the response to an NO donor was unaffected, suggesting decreased bioavailability of NO. Addition of the @entity224 radical scavenger @entity11933 restored the ability of @entity1812 , enalaprilat, and @entity3591 to suppress @entity26 consumption in tissue from 23-mo-old animals to levels seen in younger animals, suggesting NO destruction by @entity224 as the reason for decreased NO availability. @entity12824 , an inhibitor of @entity1110 oxidase, similarly restored the ability of all three drugs to suppress @entity26 consumption, suggesting @entity1110 oxidase as the enzyme responsible for enhanced @entity224 production in aging. Levels of eNOS protein, assessed by immunoblotting, did not change significantly with age. These results suggest that NO availability is decreased in the aging kidney and that this is due to scavenging of NO by @entity224 produced by @entity1110 oxidase. Oxidant stress, by depleting NO, may contribute to the structural and hemodynamic changes characteristic of the aging kidney.
