# Renal Effects of Aldosterone

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2020 · —

## Abstract

The goal of this work is to determine how aldosterone causes cardiovascular disease, including
hypertension and heart failure. Mice in which the mineralocorticoid receptor can be deleted in
the kidney only will be used to examine aldosterone's role in signaling. These mice exhibit
diminished sodium flux through both the thiazide-sensitive NaCl cotransporter and the epithelial
sodium channel. Yet transport via the former is fully normalized when the mice are placed on
low potassium diet, indicating that sodium channel stimulation is the major direct effect of
aldosterone. The proposed experiments will test whether mineralocorticoid receptors along the
second part of the distal convoluted tubule, known as the DCT2, modulate sodium chloride
transport, but do so by occupancy with glucocorticoids, rather than by aldosterone. This will be
done by comparing effects of deleting the aldosterone synthase gene, which leads to deficient
aldosterone production, with the effects of deleting the mineralocorticoid receptor. The activity of
the sodium channel will be measured using patch clamp and whole cell recording and the
activity of the thiazide-sensitive NaCl cotransporter will be assessed using thiazide testing and
phosphor-protein analysis. If channel transport activity is low in the receptor knockout, but not
the synthase knockout, this will support the hypothesis.
In a second aim, novel mediators of aldosterone signaling will be sought. We will dissect
collecting ducts from mice with and without mineralocorticoid receptors, and consuming diets of
varied electrolyte content. These collecting ducts will be subjected to RNAseq, to determine
transcriptional differences that may underlie aldosterone effects. We will compare the transcripts
differentially expressed in high aldosterone states versus those absent in mice with low
aldosterone or lacking mineralocorticoid receptors. We will then select candidate genes to be
tested using cultured epithelial cells, and ultimately in vivo. We will seek proteins that are
essential for stimulating sodium channels under high aldosterone conditions.

## Key facts

- **NIH application ID:** 9934859
- **Project number:** 5I01BX002228-07
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** David Hoadley Ellison
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2014-01-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934859

## Citation

> US National Institutes of Health, RePORTER application 9934859, Renal Effects of Aldosterone (5I01BX002228-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934859. Licensed CC0.

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