# Synaptic Mechanisms of Stress-Induced Hypertension

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $409,622

## Abstract

Synaptic mechanisms of stress-induced hypertension
Project Summary
Hypertension is one of the most prevalent health problems and a well-recognized risk factor for many
fatal diseases. Thus, it is crucial to identify the mechanisms responsible for the development of
hypertension. Prolonged and repeated exposure to stress may cause chronic elevation of sympathetic
nerve activity, which contributes to the development of hypertension. Individuals with a genetic
predisposition to hypertension may develop a sustained elevation of arterial blood pressure even after
removal of the stressor. However, little is known about the neural mechanisms underlying chronic-
stress–induced persistent hypertension. Our long-term goal is to determine the synaptic mechanisms
involved in stress-induced hypertension. This project will use borderline hypertensive rats (BHRs), the
first-generation offspring of cross-breeding of spontaneously hypertensive rats and normotensive
Wistar-Kyoto rats, to explore the molecular mechanism responsible for chronic stress-induced
hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a key brain site that mediates
the stress response and is an important source of the excitatory drive that heightens sympathetic
vasomotor tone in the development of hypertension. The preliminary studies showed that chronic stress
increased the expression level of α2δ-1 in the PVN, which in turn interacts with the glutamate N-methyl-
D-aspartate receptor (NMDAR) to increase its synaptic activity. The central hypothesis is that chronic
stress transforms borderline hypertension into persistent hypertension through upregulation of α2δ-1 in
the PVN, which interacts with NMDARs and leads to enhanced synaptic NMDAR trafficking and
heightened sympathetic outflow. The hypothesis will be tested through pursuit of the following 3 specific
aims: 1. Determine the extent to which chronic stress upregulates the expression levels of α2δ-1 and
NMDARs in the PVN in BHRs. 2. Determine the role of α2δ-1 in the PVN in chronic stress-induced
sustained hypertension in BHRs. 3. Determine whether α2δ-1 interacts with NMDARs and the role of
α2δ-1 in enhanced NMDAR activity of PVN presympathetic neurons in BHRs with chronic stress-
induced sustained hypertension. The proposed work is innovative because it will be the first study to
investigate the interactions between α2δ-1 and NMDARs in the PVN in chronic stress–induced
hypertension. The proposed work is highly significant because it will not only identify new molecular
mechanisms underlying stress-induced hypertension but also may lead to the development of new
treatments for neurogenic hypertension.
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## Key facts

- **NIH application ID:** 9840930
- **Project number:** 5R01HL142133-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** De-Pei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,622
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840930

## Citation

> US National Institutes of Health, RePORTER application 9840930, Synaptic Mechanisms of Stress-Induced Hypertension (5R01HL142133-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9840930. Licensed CC0.

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