# Salt, Blood Pressure, and Inflammation

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $561,683

## Abstract

A high salt diet is an established cause of hypertension and cardiovascular morbidity. However, recent work
has shown that Na+ is stored, predominantly in tissues such as the skin, and that this storage both drives and
is driven by inflammation. This discovery has exposed a fundamental gap in our understanding: we do not
understand the relationship between salt, inflammation, and blood pressure in humans. It is important to fill this
gap because many inflammatory diseases remain poorly controlled and are associated with hypertension and
increased cardiovascular risk. The rationale for the research proposed is: 1) Na+ is stored in the skin; 2) skin
Na+ concentrations can be measured by 23Na magnetic resonance imaging (MRI) and are induced by excess
salt intake and associated with elevated blood pressure; 3) skin Na+ concentrations boost pro-inflammatory
immune cell responses that have beneficial effects protecting against skin infection but also have potentially
detrimental pro-inflammatory systemic effects; 4) a high dietary salt intake is pro-inflammatory and exacerbates
autoimmune disease and arthritis in animal models. A critical knowledge gap is that the effects of dietary salt
intake and tissue Na+ on inflammation and blood pressure in humans in the setting of inflammation is not
known. Our overarching hypothesis is that, in the setting of inflammation, high dietary salt intake affects
regulation of both blood pressure and inflammation adversely and does so through accumulation of skin Na+.
Accordingly, we propose to study patients with rheumatoid arthritis (RA) as a model of chronic inflammation.
RA is a prototypical, common autoimmune inflammatory disease that is associated not only with
musculoskeletal consequences but also with increased hypertension and cardiovascular mortality. We will
determine: Aim 1) if skin Na+ measured by 23Na MRI is higher in patients with active RA than in patients with
well-controlled RA and controls; and Aim 2) if a low Na+ diet in patients with RA decreases skin Na+
concentrations and improves inflammation and blood pressure. These studies will define the relationship
between dietary Na+ intake, tissue Na+ concentrations, inflammation, and blood pressure and will use a clinical
intervention (reduced salt diet) in patients to break the self-sustaining cycle between inflammation↔tissue Na+
and vascular dysfunction. The studies are innovative by moving from basic to clinical research to for the first
time: 1) use 23Na MRI to determine the vascular effects of tissue Na+ in humans in the setting of inflammation;
2) define the effect of modified salt intake on autoimmune inflammatory disease in humans. The studies
proposed have high potential impact since manipulation of dietary salt intake or tissue Na+ concentrations have
the potential to improve inflammatory autoimmune diseases as well as their cardiovascular complications in
millions of people.

## Key facts

- **NIH application ID:** 9841440
- **Project number:** 5R01HL140145-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Charles M. Stein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,683
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841440

## Citation

> US National Institutes of Health, RePORTER application 9841440, Salt, Blood Pressure, and Inflammation (5R01HL140145-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9841440. Licensed CC0.

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