# Neural control of the kidney and long-term blood pressure regulation

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $333,476

## Abstract

ABSTRACT
Hypertension is predicted to be the leading global cause of death and disability by the year 2020. The
development of antihypertensive drugs has been dramatically less productive than expected, making new
mechanistic insights into blood pressure regulation essential. This application will test the hypothesis that
mechanoreceptor dependent sympathoinhibitory afferent renal nerve reno-renal reflexes suppress sympathetic
outflow to the kidney to reduce α1-adrenoceptor stimulated NCC-mediated sodium reabsorption and counter
hypertension. These studies will employ our novel technique of selective afferent renal nerve ablation, direct
mechano- and chemosensitive stimuli, and pharmacological tools in rat models of hypertension (Aims 1, 2 &
3), a unique mouse distal convoluted tubule cell line (Aim 3) and normotensive and hypertensive human
patient samples (Aim 3) to delineate the integrated renal and sympathetic nervous system mechanisms that
influence renal sodium reabsorption to regulate long term blood pressure. The following Specific Aims will be
conducted to test this hypothesis: Specific Aim 1: The afferent renal nerve reno-renal reflex mediates
sympathoinhibition and natriuresis to prevent the initiation of salt-sensitive hypertension. Specific Aim 2: That
mechanoreceptor-dependent afferent renal nerve activation facilitates fluid and electrolyte homeostasis and
blood pressure regulation. Specific Aim 3: That norepinephrine regulates NCC activity, via an α1-adrenoceptor
gated WNK1-OxSR1 signal transduction pathway, to mediate sodium homeostasis and long-term blood
pressure regulation. These hypertension focused studies are central to the mission of the National Heart Lung
and Blood Institute (NHLBI), which is to promote the prevention and treatment of heart, lung and blood
disease, and directly support Goal 1 of the NHLBI Strategic Plan, which is to improve understanding of
molecular and physiological basis of health and disease. These studies also directly address the 2014 NHLBI
Salt in Human Health and Sickness Working Group recommendations for 1) a need to further illuminate the
biological mechanisms and pathological processes to which salt may contribute, and 2) the identification of
salt-sensitive hypertension as a priority research topic. Specific Aim 1 will establish a role of the afferent renal
nerves in sodium excretion, sympathetic outflow and blood pressure regulation during acute and chronic
challenges to salt and water balance. Specific Aim 2 will establish the renal mechanoreceptors as the site of
afferent renal nerve signal propagation to the brain to facilitate sympathoinhibition and sodium excretion.
Specific Aim 3 will establish the actions of the sympathetic nervous system release of norepinephrine to
regulate the sodium chloride cotransporter, via a novel α1- adrenoceptor signal transduction pathway in rat and
human studies. Our studies, performed by a multidisciplinary collaborative research team, will potentially
id...

## Key facts

- **NIH application ID:** 10176175
- **Project number:** 5R01HL139867-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Richard David Wainford
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $333,476
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176175

## Citation

> US National Institutes of Health, RePORTER application 10176175, Neural control of the kidney and long-term blood pressure regulation (5R01HL139867-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176175. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*