# Control of Renal Inflammation in Hypertension

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2022 · $542,401

## Abstract

PROJECT SUMMARY
By 2025, an estimated 1.6 billion people around the world will be hypertensive. This estimate may be higher
given recently modified guidelines for hypertension that are inclusive of millions of additional patients. What is
concerning is that almost 20% of all hypertensive patients are resistant to current therapies. Better understanding
of the underlying mechanisms involved in the pathogenesis of hypertension is required in order to identify new
and effective therapeutic strategies.
Chronic renal inflammation is suspected to be a causal mechanism of resistant hypertension. The objective of
this grant proposal is to examine the the control of renal inflammation using a model of chronic inflammatory
disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory in which renal inflammation
precedes the development of hypertension in SLE; therefore, it is an appropriate disease model to use to
elucidate mechanisms involved in the inflammatory origins of hypertension.
Endogenous neuro-immunoregulatory systems like the novel cholinergic anti-inflammatory pathway are involved
in the normal control of excessive inflammation. Our data indicate that boosting this vagus nerve-to-spleen
pathway via systemic pharmacological approaches reduces renal inflammation and blood pressure in an
experimental mouse model of SLE. Based on this, we hypothesize that active neuroimmune pathways protect
the kidney by suppressing renal inflammation and preventing the subsequent development of
hypertension. In Aim 1 of this proposal, we will determine if central stimulation of the vagus nerve via both
chemogenetic and pharmacological techniques reduces renal inflammation through the cholinergic anti-
inflammatory pathway, and is antihypertensive in SLE. Studies in this aim will elucidate central nuclei involved
in the regulation of renal inflammation that if left unchecked can result in hypertension in SLE. In Aim 2, we will
determine whether inhibiting the cholinergic anti-inflammatory pathway by blocking its nodes of
neurotransmission exacerbates SLE hypertension. Studies in this aim will determine critical neural/peripheral
components necessary for proper neuroimmune regulation. In Aim 3, we will determine if an intrinsic renal anti-
inflammatory pathway works in parallel with the spleen-centric cholinergic anti-inflammatory pathway. Studies in
this aim will examine the anti-inflammatory potential of local acetylcholine in renal immune cells in hypertension-
prone SLE mice using in vitro studies and innovative sniffer cell technoogy. Overall, the proposed studies will
explain how homeostatic neuroimmune mechanisms control renal inflammation in health, as well as offer
therapeutic options for controlling renal inflammation in hypertension and other chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 10405490
- **Project number:** 5R01HL153703-02
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** KEISA WILLIAMS MATHIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $542,401
- **Award type:** 5
- **Project period:** 2021-05-14 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405490

## Citation

> US National Institutes of Health, RePORTER application 10405490, Control of Renal Inflammation in Hypertension (5R01HL153703-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10405490. Licensed CC0.

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