# Dietary sodium, inflammation, and salt sensitivity of blood pressure

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $734,723

## Abstract

PROJECT SUMMARY/ABSTRACT
Salt sensitivity of blood pressure (SSBP) is defined as the change in blood pressure (BP) in relation to change
in salt intake. An increase in BP from low- to high-salt diet is common and associated with an increased risk of
cardiovascular morbidity and mortality, even among normotensive individuals. Yet, the pathophysiology of
SSBP is not well understood. The prevailing paradigm is that abnormalities of neurohormones that regulate
sodium (Na+) retention and excretion and/or Na+ transporting pathways create Na+ imbalances that underlie
susceptibility to SSBP. As a homeostatic mechanism, BP fluctuates to maintain Na+ balance, i.e. higher BP is
needed for pressure natriuresis to excrete excess Na+. An alternate framework emphasizes vascular
dysregulation as the inciting mechanism. In both constructs, how Na+ itself influences BP remains
incompletely understood. Our preliminary work suggests that excess Na+ induces a pro-inflammatory state
that sustains higher BP. Interleukin-6 (IL-6) drives the induction of interleukin-17 (IL-17) secreting T helper 17
cells that were recently demonstrated to be pathogenic in response to Na+ exposure. IL-6, IL-17 and related
cytokines regulate renal Na+ transporters and raise BP through vascular inflammation, fibrosis, and impaired
vasodilation. The immune response to high- and low-salt diet in humans, however, is not completely
understood, emphasizing the need for more detailed human studies, with deeper immune profiling under
controlled salt conditions and with neurohormonal assessment. Our overarching postulate is that the
inflammatory response to excess dietary salt intake is associated with SSBP. The Coronary Artery Risk
Development in Young Adults (CARDIA) study is the ideal cohort in which to translate our preliminary findings.
We propose to investigate SSBP in CARDIA using standardized low- and high-salt diets and 24-hour
ambulatory BP monitoring. We will quantify SSBP in a total of 500 participants from the Chicago and
Birmingham field centers during the upcoming year 35 exam (beginning in 2020). Our specific aims are: 1) to
define the distribution of SSBP and its clinical correlates in a contemporary community-based US cohort of
middle-aged individuals; 2) to investigate the immune response to dietary salt loading, and 3) to investigate the
association between the immune and BP responses to dietary salt loading. The proposed study represents a
unique opportunity to leverage a large, well-phenotyped cohort to test novel hypotheses regarding SSBP.
Phenotyping SSBP using standardized high- and low-salt diets in CARDIA will be novel as this has never been
performed in any of the existing US based NHLBI sponsored cardiovascular epidemiologic cohorts. The
proposed work has the potential to yield a more readily available approach for differentiating an individual as
salt-sensitive or resistant. New insights into the pathophysiology of SSBP should also provide a foundation for
investigatin...

## Key facts

- **NIH application ID:** 10200882
- **Project number:** 5R01HL148661-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** NORRINA Bai ALLEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $734,723
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200882

## Citation

> US National Institutes of Health, RePORTER application 10200882, Dietary sodium, inflammation, and salt sensitivity of blood pressure (5R01HL148661-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10200882. Licensed CC0.

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