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Mechanism of Protection of the Aldosterone Signaling Pathway in the Rat Collecting Duct during Pregnancy
Author(s) -
West Crystal,
Masilamani Shyama ME
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1097.7
Subject(s) - medicine , endocrinology , aldosterone , mineralocorticoid receptor , kidney , receptor , stimulation , mineralocorticoid , chemistry , epithelial sodium channel , biology , sodium , organic chemistry
Recently, we found that renal epithelial sodium channel (ENaC) protein and activity are increased in the late pregnant (LP) rat, via a mineralocorticoid receptor (MR)‐mediated mechanism. The aim of this study is to examine the mechanism of protection of MR‐mediated ENaC stimulation in pregnancy when circulating cortisol and progesterone are also increased, two factors known to interfere with MR‐mediated effects. We measured serum and renal levels of aldosterone and progesterone using RIA assays in virgin (V, n=14) and LP (n=8) rats. Further, we determined whole kidney protein abundance of the progesterone receptor (PR) and of the enzyme 11β HSD2 which metabolizes cortisol. Plasma aldosterone (V= 0.82±0.14; LP=2.31±0.32 nmol/L, p<0.05) and renal aldosterone (V=0.82 ± 0.06; LP=1.62 ± 0.22, nmol/L/g kidney), p<0.05) were increased with pregnancy. Interestingly, plasma progesterone increased (V=102 ± 11; LP=182 ± 9, nmol/L), p<0.05) while renal progesterone did not change (V=358 ± 61; LP=339 ± 66, nmol/L/g kidney, NS). Although PR abundance was unchanged (LP= 94±6 % of virgin n=7, NS), we found an increase in 11βHSD2 abundance (LP=135±5 % of virgin n=7, p<0.05). Thus renal MR‐mediated effects are protected in pregnancy in part by 1) increasing cortisol metabolism via increased 11βHSD and 2) preventing competitive inhibition of the MR by renal adaptations that prevent an increase in local progesterone levels.