Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.
Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.
West
Crystal
C
Department of Internal Medicine/Division of Nephrology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0160, USA.
Zhang
Zheng
Z
Ecker
Geoffrey
G
Masilamani
Shyama M E
SM
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D000077545:Eplerenone; D005260:Female; D015151:Immunoblotting; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D008901:Mineralocorticoids / Q000378:metabolism; D009318:Natriuresis; D010953:Plasma Volume; D011247:Pregnancy; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation
D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; C440894:Scnn1a protein, rat; D026941:Sodium Channel Blockers; C013407:benzamil; D013148:Spironolactone; D000077545:Eplerenone; D000584:Amiloride; D012964:Sodium