# Intermittent hypoxia and hypertension: Role of the lamina terminalis

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2022 · $680,469

## Abstract

The central objective of this research program is to determine the role of the CNS in hypertension associated
with chronic intermittent hypoxia (CIH), a model of hypoxemia associated with sleep apnea. Our previous results
indicate that the median preoptic nucleus (MnPO) contributes to the sustained hypertension produced by CIH in
rat. These experiments will investigate 3 novel mechanisms that may allow the MnPO to contribute to CIH
hypertension. Our working hypothesis, based on our previous studies, is that CIH triggers FosB transcriptional
activity involving angiotensin II (ANG II) and NO signaling to increase excitation causing BDNF-driven increases
in intracellular chloride. These effects would further increase excitation and reduce or reverse inhibition from
arterial baroreceptors promoting sustained CIH HTN during normoxic periods of the day.
Specific Aim 1: Test the role of angiotensin signaling in increased MnPO excitation in CIH HTN.
Hypothesis: Increased angiotensin signaling increases the activity of PVN-projecting MnPO neurons.
Aim 1 will quantify the contribution of the brain angiotensin system to increased activity in PVN-projecting MnPO
neurons using angiotensin “sniffer cells” 19 combined with optogenetics, patch clamp electrophysiology, in vivo
recording of sympathetic nerve activity, and MnPO single unit activity.
Specific Aim 2: Test the role of NO in increasing MnPO excitation in CIH HTN.
Hypothesis: Increased expression and activity of nos1 in MnPO increases presynaptic excitation to drive
sustained CIH hypertension.
Aim 2 will test the hypothesis that the increase of nos1 expression and activity triggered by CIH increases
presynaptic excitation in PVN projecting MnPO neurons. This mechanism will be tested using in vitro
electrophysiology and paired real-time measurements of NO with carbon fiber electrodes and DAF-2 imaging, in
vivo recording of sympathetic nerve activity, and chronic blood pressure recording with radio telemetry.
Specific Aim 3: Determine the contribution of reduced/reversed GABA inhibition and BDNF to changes in
MnPO excitability, synaptic efficacy, and CIH HTN.
Hypothesis: CIH triggers BDNF neurons that reduces/reverses GABA inhibition in MnPO neurons.
Aim 3 will determine if BDNF reduces/reverses baroreceptor inhibition by GABA in PVN-projecting MnPO
neurons though chloride transports such as sodium potassium chloride cotransporter 1 (NKCC1) and/or
potassium chloride cotransporter2 (KCC2). These experiments will use live cell chloride imaging, brain slice and
in vivo electrophysiology, and channel rhodopsin assisted circuit mapping.

## Key facts

- **NIH application ID:** 10330441
- **Project number:** 5R01HL155977-02
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** J Thomas Cunningham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $680,469
- **Award type:** 5
- **Project period:** 2021-01-18 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330441

## Citation

> US National Institutes of Health, RePORTER application 10330441, Intermittent hypoxia and hypertension: Role of the lamina terminalis (5R01HL155977-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330441. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*