Pregnancy upregulates the α subunit of the amiloride‐sensitive epithelial sodium channel (ENaC) in rat kidney

A normal, healthy pregnancy is associated with marked sodium retention and extracellular fluid volume expansion. The renal mechanisms responsible for this pregnancy‐associated sodium retention are not understood. To address this, we used semiquantitative immunoblotting and real‐time RT‐PCR to examine sodium transporter and channel regulation along the renal tubule in the pregnant rat. Whole kidney homogenates from age‐matched control and pregnant female rats (early‐pregnancy (day 6–8), mid‐pregnancy (day 11–13), and late‐pregnancy (day 18–19)) were compared. The protein abundance of the α subunit of ENaC (amiloride‐sensitive sodium channel) was significantly increased at all three stages of pregnancy (early pregnant = 143.32 ± 13.31*; mid pregnant = 167.04 ± 28.90*; late pregnant = 167.63 ± 16.60*; % of control, * vs control, p<0.05) while the mRNA abundance of the α subunit of ENaC did not change (early = 93.29 ± 6.36, mid = 140.84 ± 15.45, late = 113.33 ± 22.20, % of control, NS) during pregnancy. Additionally, there was no increase in the protein abundance of NHE3 (Na‐H exchanger‐type 3), NKCC2 (bumetanide‐sensitive Na‐K‐2Cl cotransporter), NCC (thiazide‐sensitive cotransporter Na‐Cl cotransporter), or β and γ subunits of ENaC. These data demonstrate an upregulation of the αsubunit of ENaC (the rate‐limiting subunit for sodium channel formation) during pregnancy which could in part contribute to the pregnancy‐associated sodium retention. This work was supported by the NHLBI K22 award.