# Identification of mechano versus chemo-sensitive renal sensory neurons in hypertension

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $588,804

## Abstract

ABSTRACT
Renal denervation lowers arterial blood pressure in multiple clinical trials and experimental animal
models of hypertension. These anti-hypertensive effects have been partly attributed to the
removal of renal sensory nerves as selective denervation of renal sensory nerves lowers arterial
blood pressure to the same extent as total renal denervation. Despite our current knowledge of
renal nerves, there is a severe lack of anatomical, functional, and mechanistic knowledge about
the specific sensory fiber-types responsible for cardiovascular control. Renal sensory nerves
detect mechanical and chemical stimuli within the kidneys and consequently alter sodium
reabsorption, renin secretion, and sympathetic outflow. These responses are dependent on
mechano- and chemo- sensitive nerve fibers which have not been clearly defined. Our preliminary
data using single-cell transcriptomics on renal sensory neurons demonstrates the existence of
two distinct populations: the mechanosensitive channel Piezo2 and chemosensitive channel
TRPV1. The overall hypothesis of this proposal is that neurochemically distinct populations of
renal sensory neurons expressing Piezo2 and TRPV1 mediate mechano- and chemo-sensitive
responses in the kidney. The neurochemical profile of these neurons switches in renal stenosis
from a loss of Piezo2-mechanosensitive fibers to robust expression and increased sensitivity of
TRPV1-chemosensitive fibers to elevated sympathetic outflow and arterial blood pressure. Aim 1
will employ in vivo single-unit recordings, single-cell transcriptomics (>40 sensory genes), and
optogenetics to determine the extent by which Piezo2 and TRPV1-expressing neurons represent
mechano- and chemo- sensitive renal sensory nerve populations. Aim 2 will determine how
hypertension produced by renal stenosis alters the mechano- versus chemosensitivity of renal
afferents, the neurochemical profile of sensory neurons, and the sensory innervation of the
kidney. Aim 3 will directly assess the contribution of Piezo2 versus TRPV1 renal sensory fibers
and channels to renal sensory function and renovascular hypertension. This proposal will define,
for the first time, the neurochemical and functional phenotype of renal sensory nerve populations
involved in the control of arterial blood pressure, anatomically map innervation sites in the kidney,
and functionally test distinct renal afferent fibers populations and channels in vivo that have a
pathological role of hypertension.

## Key facts

- **NIH application ID:** 10130622
- **Project number:** 5R01HL152680-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** SEAN D STOCKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $588,804
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130622

## Citation

> US National Institutes of Health, RePORTER application 10130622, Identification of mechano versus chemo-sensitive renal sensory neurons in hypertension (5R01HL152680-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10130622. Licensed CC0.

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