# Circadian control of sodium excretion

> **NIH NIH P01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $489,794

## Abstract

PROJECT 1 SUMMARY
 High salt diets have grown increasingly prevalent in the Western world and contribute to increased risk of
cardiovascular disease including hypertension and chronic kidney disease. The renal endothelin system has
emerged an important control system for sodium and water excretion and so derangements in this pathway
could provide insights for potential new therapeutic approaches. Abnormalities in circadian rhythms are
associated with increased risk of a wide range of metabolic, cardiovascular, and other disorders. Furthermore,
cardiovascular events are far more prevalent at specific times of day suggesting a circadian contribution of
cardiovascular disease. Recent studies have revealed that the peripheral molecular clock regulates water and
sodium homeostasis, but the underlying mechanisms are unclear. We recently observed that Bmal1, a
circadian-dependent transcription factor, loses its rhythmicity under high salt diet conditions and appears to be
regulated by the endothelin (ET) system. Rats lacking a functional ETB receptor have a severely delayed
response to an acute salt load that is dependent upon the time of day. Therefore, our goal is to determine the
relationship between the ET-1 system and circadian regulation of sodium excretion. Aim 1 is designed to test
the hypothesis that ETB receptor activation suppresses Bmal1 to facilitate sodium excretion and account for
diurnal renal sodium handling. Aim 2 will test the hypothesis that Bmal1 functions to suppress sodium
excretion. We have also uncovered that female rats are protected against the loss of excretory control in a
diurnal manner that may be due to differences in sex steroid function. Thus, Aim 3 will test the hypothesis that
the balance between effects of testosterone and estrogen effects on vascular ETA receptor function accounts
for sex differences in diurnal control of sodium excretion.

## Key facts

- **NIH application ID:** 10136708
- **Project number:** 5P01HL136267-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** DAVID M POLLOCK
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $489,794
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136708

## Citation

> US National Institutes of Health, RePORTER application 10136708, Circadian control of sodium excretion (5P01HL136267-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10136708. Licensed CC0.

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