# Neuroendocrine dysfunction and hypertension

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $614,144

## Abstract

Project Summary
Hypertension is a high-risk factor for stroke, cardiovascular diseases, and renal failure and it is one of the
leading causes of death in the US and afflicts 75 million people. Primary hypertension, the most common form
of hypertension, is associated with elevated sympathetic vasomotor tone and hyperactivity of the hypothalamic
pituitary adrenal (HPA) axis. However, the role of hyperactivity of the HPA axis in elevated sympathetic outflow
in primary hypertension remains largely unknown. The paraventricular nucleus (PVN) of the hypothalamus is a
critical brain region that integrates neuroendocrine and cardiovascular functions. In primary hypertension, PVN
presympathetic neuron activity is increased and provides excitatory drive to maintain heightened sympathetic
vasomotor tone. Glutamatergic synaptic inputs to the PVN presympathetic neurons are enhanced in
spontaneously hypertensive rats (SHRs). However, the cellular mechanisms underlying hyperactivity of PVN
presympathetic neurons and enhanced excitatory synaptic inputs in SHRs remain unknown. The
corticotrophin-releasing hormone (CRH)-containing neurons in the PVN (PVN-CRH neurons) are an essential
component of the HPA axis. PVN-CRH neurons are activated in hypertension as indicated by increased
expression levels of CRH protein and mRNA levels in the PVN in patients with primary hypertension. The
objective of this project is to determine the role of PVN-CRH neurons in regulating blood pressure and
sympathetic outflow in primary hypertension. Our pilot study found that PVN-CRH neuron activity was
increased in SHRs, and selective inhibition or ablation of PVN-CRH neurons decreased arterial blood pressure
in SHRs. In addition, selective inhibition of PVN-CRH neurons suppressed the activity of PVN presympathetic
neurons in SHRs; the effect was eliminated by blocking CRH receptor 1. Thus, we will test our central
hypothesis that increased activity of PVN-CRH neurons leads to hyperactivity of PVN presympathetic neurons
and elevated sympathetic outflow in primary hypertension. We will first determine if hyperactivity of PVN-CRH
neurons is required for high blood pressure and elevated sympathetic outflow in primary hypertension (Aim 1).
We will also identify the synaptic mechanism underlying hyperactivity of PVN-CRH neurons in hypertension
(Aim 2). Finally, we will determine the role of PVN-CRH neurons in the elevated activity of PVN presympathetic
neurons and enhanced glutamatergic synaptic inputs in hypertension (Aim 3). Our proposed studies will greatly
improve the understanding of the cellular and molecular mechanisms underlying primary hypertension. We
expect our studies to provide novel information about the neuronal mechanisms responsible for primary
hypertension and an important rationale for developing novel treatment strategies to reduce sympathetic
vasomotor tone in primary hypertension.

## Key facts

- **NIH application ID:** 10280320
- **Project number:** 1R01HL159157-01
- **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:** $614,144
- **Award type:** 1
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10280320

## Citation

> US National Institutes of Health, RePORTER application 10280320, Neuroendocrine dysfunction and hypertension (1R01HL159157-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10280320. Licensed CC0.

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