Increased Epithelial Sodium Channel Activity Contributes to @entity101 Caused by XXXX - Cotransporter Electrogenic 2 Deficiency.

@entity3529 @entity4024 @entity101 @entity918 @entity19 @entity6478 @entity5993 @entity28919 @entity72089 @entity164 @entity4202
UNASSIGNED: The gene @entity72089 encodes the @entity5993 cotransporter electrogenic 2, which is located in the distal nephron. Genetically deleting @entity5993 cotransporter electrogenic 2 (knockout) causes @entity4024 -retention and @entity101 , a phenotype that is diminished with alkali loading. We performed experiments with acid-loaded @entity19 and determined whether overactive epithelial @entity4024 channels ( @entity28919 ) or the @entity4202 cotransporter causes the @entity4024 retention and @entity101 in knockout. In untreated @entity19 , the mean arterial pressure was higher in knockout, compared with @entity164 ( @entity164 ); however, treatment with @entity6478 , a blocker of @entity28919 , abolished this difference. In contrast, @entity918 , an inhibitor of @entity4202 cotransporter, decreased mean arterial pressure in @entity164 , but not knockout. Western blots showed that quantity of plasmalemmal full-length @entity28919 -a was significantly higher in knockout than in @entity164 . @entity6478 treatment caused a 2-fold greater increase in @entity4024 excretion in knockout, compared with @entity164 . In knockout, but not @entity164 , @entity6478 treatment decreased plasma [ @entity4024 ] and urinary @entity3529 excretion, but increased hematocrit and plasma [ @entity3529 ] significantly. Micropuncture with microelectrodes showed that the [ @entity3529 ] was significantly higher and the transepithelial potential (Vte) was significantly lower in the late distal tubule of the knockout compared with @entity164 . The reduced Vte in knockout was @entity6478 sensitive and therefore revealed an upregulation of electrogenic @entity28919 -mediated @entity4024 reabsorption in this segment. These results show that, in the absence of @entity5993 cotransporter electrogenic 2 in the late distal tubule, acid-loaded @entity19 exhibit disinhibition of @entity28919 -mediated @entity4024 reabsorption, which results in @entity4024 retention, @entity3529 wasting, and @entity101 .
