# Prostaglandin E2, Immunity and hypertension

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $395,000

## Abstract

Prostaglandins (PGs), oxidative metabolites of arachidonic acid, mediate an array of physiologic functions
including inflammation and systemic blood pressure homeostasis. Prostaglandin E2 (PGE2) is a major regulator
of blood pressure, where it exerts pro-hypertensive or anti-hypertensive effects depending upon the setting.
These physiologically opposing effects are mediated by four PGE2 receptors, designated the E-Prostanoid
(EP) receptors EP1 to EP4. Previous work by our group and others determined that EP1 and EP3 primarily
mediate the pro-hypertensive response, while EP2 and EP4 receptors mediate the anti-hypertensive response.
PGs are well characterized to be effectors of inflammation, and thus PGs act at the intersection of inflammation
and blood pressure homeostasis, making them potential targets in the etiology of essential hypertension. Our
hypothesis is that EP receptors regulate immune-inflammatory cells and a robust T-cell mediated immune
response contributes to hypertension. Moreover, multiple, repeated stimulation of the T-cell response in the
face of hypertensive stimuli such as salt loading is modulated by PGs to generate sustained elevated blood
pressure. We hypothesize that the EP3 receptor is the principal receptor facilitating the PGE2 response to raise
blood pressure. To test these related hypotheses we propose three Specific Aims: 1) Test the hypothesis that
EP3 regulates the response to repeated pro-hypertensive stimuli leading to the development of memory T-cells
underlying sustained elevation of blood pressure; 2) Test the hypothesis that elevated ROS leads to
neoantigen stimulated T-cell formation; 3) Test the hypothesis that EP receptor expression on T-cells
contributes to the generation of hypertension.

## Key facts

- **NIH application ID:** 9846243
- **Project number:** 5R01HL134895-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** RICHARD M. BREYER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846243

## Citation

> US National Institutes of Health, RePORTER application 9846243, Prostaglandin E2, Immunity and hypertension (5R01HL134895-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9846243. Licensed CC0.

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