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Coordinated regulation of ENaC activity in the distal nephron by aldosterone and Ang II (1088.14)
Author(s) -
Mamenko Mykola,
Zaika Oleg,
Prieto Minolfa,
Jensen Behrana,
Doris Peter,
Navar Gabriel,
Pochynyuk Oleh
Publication year - 2014
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.28.1_supplement.1088.14
Subject(s) - epithelial sodium channel , aldosterone , endocrinology , medicine , natriuresis , stimulation , chemistry , reabsorption , angiotensin ii , renin–angiotensin system , mineralocorticoid , renal sodium reabsorption , nephron , sodium , kidney , receptor , blood pressure , organic chemistry
Recent studies point to direct actions of Ang II on ENaC‐mediated Na + reabsorption in the distal nephron via stimulation of AT 1 R that occurs independently of aldosterone‐MR signaling. We used split‐opened distal nephrons from mice to probe the interaction between aldosterone and Ang II cascades in controlling ENaC activity during variations in dietary salt intake and in Ang II‐induced hypertension. Systemic MR inhibition abolished increases in the numbers of functionally active ENaC in response to low Na + diet. Simultaneous inhibition of MR and AT 1 R at low dietary salt intake not only reduced the amount of active channels, but also decreased ENaC open probability and produced significantly greater natriuresis than either treatment alone. Chronic Ang II infusion stimulated ENaC activity greatly above levels observed during dietary sodium restriction. Importantly, maximal MR inhibition failed to suppress ENaC activity to control values. In contrast, blocking of de novo Ang II synthesis with captopril abolished stimulation of ENaC activity in Ang II infused animals. We conclude that during variations in dietary salt intake both aldosterone and Ang II contribute complementarily to the regulation of ENaC activity. In contrast, aldosterone‐independent stimulation of ENaC activity mediated by ACE dependent endogenous intratubular Ang II formation predominates in the setting of Ang II‐induced hypertension. Grant Funding Source : DK095029