# Cardiac afferents and renal function in heart failure

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $571,665

## Abstract

Project Summary
Chronic heart failure (CHF) is a growing epidemic in western societies. In the United States alone,
approximately 6 million people live with CHF. In late stage CHF, renal failure is a complication that results in
worsening heart failure. Patients exhibiting the cardio-renal syndrome have an extremely poor prognosis.
Medical therapy for this syndrome has been ineffective. A new way of thinking about the mechanisms
responsible for worsening renal function in CHF is necessary. During the previous cycle of this grant we
elucidated an important neural pathway that not only mediates cardiac remodeling but also drives a massive
increase in cardiac, renal and global sympathetic nerve activity in CHF. Ablation of this pathway markedly
improves survival in the post MI-CHF rodent model. The Cardiac Sympathetic Afferent Reflex (CSAR) is
mediated, in large part, by epicardial, TRPV1 receptor-expressing sensory endings whose cell bodies reside in
the thoracic dorsal root ganglia. Here, we propose to build on our previous work by demonstrating an important
role for cardiac spinal afferents in mediating renal dysfunction in severe CHF. Based on our preliminary data
and using a novel TRPV1 Cre rat coupled with chemogenetic excitation and inhibition we will demonstrate the
important role that these afferents play in the pathogenesis of the cardio-renal syndrome. We will furthermore
utilize the ultrapotent neurotoxin resiniferatoxin (RTX; TRPV1 specific) to therapeutically salvage renal function
in CHF. These studies are highly relevant to the clinical situation and will pave the way for a novel and
innovative alternative to conventional therapy.

## Key facts

- **NIH application ID:** 10084301
- **Project number:** 5R01HL126796-06
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** HANJUN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $571,665
- **Award type:** 5
- **Project period:** 2015-12-18 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084301

## Citation

> US National Institutes of Health, RePORTER application 10084301, Cardiac afferents and renal function in heart failure (5R01HL126796-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10084301. Licensed CC0.

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