# Endothelial Epoxygenase, Kidney Injury, and Blood Pressure Regulation

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2024 · $494,087

## Abstract

Epidemiological and outcomes studies in patients, as well as studies in rodent models, reveal that renal ischemic
kidney injury and unilateral obstructive uropathy brings on long-term consequences: hypertension and chronic
kidney disease. Major pathophysiological contributors include impaired renal hemodynamics, endothelial dilator
dysfunction, and endothelial cell inflammation. Because the renal microcirculation lacks efficient regenerative
capacity, acute damage to the microcirculation can lead to long-term changes in renal hemodynamics that
predispose patients to hypertension and chronic kidney disease.
A class of arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs) increase renal blood flow and improve
endothelial cell function. Not known is the contribution of CYP2C epoxygenases, soluble epoxide hydrolase
(sEH), and regioisomeric EETs to salt-sensitive hypertension and chronic kidney disease following obstructive
uropathy and renal ischemic injury. We hypothesize that decreased endothelial EET levels result in endothelial
dysfunction and impaired renal hemodynamics following renal ischemic injury or urinary tract obstruction.
The immediate goals of this project are to determine the ability for endothelial EETs to improve endothelial-
dependent afferent arteriolar dilation, to decrease endothelial inflammation, and to prevent salt-sensitive
hypertension and chronic kidney disease following unilateral ureter obstruction (UUO) or ischemia/reperfusion
(I/R) kidney injury. This project will utilize pharmacological as well as global and tissue-specific genetic
manipulation of CYP2C, sEH, and EETs.
We will obtain our immediate goals by completing three aims.
Aim 1 will test the hypothesis that decreased EET levels or EET function contributes to the development of salt-
sensitive hypertension and chronic kidney disease following UUO or I/R kidney injury.
Aim 2 will test the hypothesis that increasing endothelial EET levels will improve renal microvascular endothelial
function following UUO or I/R kidney injury to prevent salt-sensitive hypertension and chronic kidney disease.
Aim 3 will test the hypothesis that pharmacological approaches to increase EET levels can prevent the long-term
salt-sensitive hypertensive and chronic kidney injury following UUO or I/R kidney injury.
Accordingly, our findings promise to advance the field forward by not only enhancing our understanding of the
pathophysiological mechanisms whereby UUO or I/R kidney injury leads to chronic kidney disease but also
leading to new therapeutic treatments.

## Key facts

- **NIH application ID:** 10842434
- **Project number:** 5R01DK126452-05
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** John D Imig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $494,087
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842434

## Citation

> US National Institutes of Health, RePORTER application 10842434, Endothelial Epoxygenase, Kidney Injury, and Blood Pressure Regulation (5R01DK126452-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842434. Licensed CC0.

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