# Integrating novel mechanisms controlling sodium excretion and blood pressure

> **NIH NIH P01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $2,291,308

## Abstract

OVERALL – PROJECT SUMMARY
The long-term goal of this Program Project Grant (PPG) is to generate new information about how fluid-
electrolyte balance is regulated and thus contributes to blood pressure control. Our studies largely focus on
mechanisms related to endothelin-1 (ET-1) and its associated receptors, ETA and ETB. Previous studies from
investigators on the project team revealed a significant role for this system in controlling renal handling of salt
and water balance, control of renal hemodynamics, and blood pressure regulation. Investigators have
demonstrated that defects in this system results in hypertension that is highly sensitive to dietary salt intake.
This is a complicated yet powerful system that balances the vasodilatory and pro-natriuretic actions of the ETB
receptor with the vasoconstrictor pro-inflammatory effects of ETA receptor activation. Exploring both renal
tubular actions, primarily in the collecting duct, along with hemodynamic effects represents a diverse approach
that is unique to this PPG. Our proposed program has several major themes that seek to elucidate novel
mechanisms of renal control of sodium handling. In Project 1, we have evidence that ET-1 contributes to
circadian regulation of blood pressure, and so we will explore how ET-1 impacts sodium excretion at different
times of day. Project 2 will closely examine how alterations in renal tubular fluid flow that are associated with
varying body fluid volume status modulate production of ET-1 within the collecting duct system and how it is
regulated by the primary cilia, polycystins and other mediators. Recent findings from Project 3 have
demonstrated a unique regulatory system involving acetylation and deacetylation of NOS1 in the collecting
duct that impacts sodium handling and salt-dependent changes in blood pressure. Furthermore, both NOS1
and NOS3 are expressed in principal cells of the collecting duct, and so we have proposed a novel hypothesis
whereby these two enzymes are regulating different aspects of cellular function. In addition, Projects 2 and 3
investigate how NOS1 and NOS3 in the collecting duct modulate both ET-1 production and actions. Finally,
two cores support this PPG: the administrative core and the animal and analytical core. The administrative
core manages and coordinates overall PPG activities, provides financial accounting and budgetary support,
schedules and arranges meetings of PPG investigators, and manages statistical analysis and data
management activities. Core B, the animal and analytical core, is responsible for managing breeding and
genotyping for rodents in all three projects. In conclusion, these studies are expected to uncover important
regulatory pathways that will aid our understanding of fluid-electrolyte and blood pressure control in health and
in disease.

## Key facts

- **NIH application ID:** 10136682
- **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:** $2,291,308
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136682

## Citation

> US National Institutes of Health, RePORTER application 10136682, Integrating novel mechanisms controlling sodium excretion and blood pressure (5P01HL136267-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136682. Licensed CC0.

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