# Mechanisms of Stress-Induced Hypertension

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $410,631

## Abstract

Mechanisms of stress-Induced Persistent Hypertension
PROJECT SUMMARY
Prolonged and persistent stress is a known risk factor in the development of hypertension. Previous stud-
ies have shown that in borderline hypertension, chronic stress-induced increases in arterial blood pressure
last for a long period after termination of stress paradigms. However, the underlying mechanisms remain
unknown. Chronic stress activates corticotropin-releasing hormone (CRH)-expressing neurons in the hypo-
thalamus and central nucleus of the amygdala (CeA), which play a key role in regulating autonomic and
cardiovascular functions during psychological stress, fear, and anxiety. The overall objective of our project
is to determine the role of CeA-CRH neurons in the development of persistent hypertension and the mech-
anisms involved. Our preliminary data showed that selectively inhibiting CeA-CRH neurons through a
chemogenetic approach prevented chronic stress-induced hypertension in borderline hypertensive rats
(BHRs) and that hyperactivity of CeA-CRH neurons was due to a reduction of K+ channel activity resulting
from stress-induced increases in histone deacetylase (HDAC) activity. Our pilot study also showed that in-
hibition of HDAC activity in the CeA in chronically stressed rats restored K+ expression and decreased fir-
ing activity of CeA-CRH neurons. In this proposal, we will test the central hypothesis that hyperactivity of
CeA-CRH neurons is responsible for stress-induced hypertension in BHRs and that a reduction in K+
channel activity caused by stress-induced upregulation of HDAC leads to hyperactivity of CeA-CRH neu-
rons in stress-induced hypertension. Because the chronic unpredictable mild stress rat model closely re-
sembles precipitation of depression by chronic and low-grade stressors in humans, this model will be used
to test the hypothesis. We have 4 specific aims: We will attempt to determine the role of CeA-CRH neurons
in the sustained hypertension in chronically stressed BHRs (aim 1), determine the role of CeA-CRH neu-
rons in regulating blood pressure and sympathetic outflow in chronically stressed BHRs (aim 2), determine
the role of K+ channels in the CeA in hyperactivity of CeA-CRH neurons and heightened sympathetic out-
flow in chronically stressed BHRs (aim 3), and identify the epigenetic mechanisms involved in long-lasting
downregulation of K+ channels in chronically stressed BHRs (aim 4). Our proposal is innovative because
findings from our proposal are expected to provide novel information about the cellular and molecular
mechanisms responsible for stress-induced persistent hypertension in borderline hypertension. This new
information is significant because it may provide an important rationale for development of new strategies
to treat neurogenic hypertension.

## Key facts

- **NIH application ID:** 10084924
- **Project number:** 5R01HL139523-04
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** De-Pei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,631
- **Award type:** 5
- **Project period:** 2017-12-28 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084924

## Citation

> US National Institutes of Health, RePORTER application 10084924, Mechanisms of Stress-Induced Hypertension (5R01HL139523-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10084924. Licensed CC0.

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