# Neuroimmune contributions to hypertension sensitization in a preclinical model of PTSD

> **NIH NIH F30** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $42,403

## Abstract

PROJECT SUMMARY
 Post-traumatic stress disorder (PTSD) is a devastating psychiatric disorder that afflicts more than
7% of all Americans across their lifespan. PTSD increases the risk for inflammatory cardiovascular
diseases, such as hypertension, but the etiology of this increased predilection for hypertension after
trauma is unknown. Both PTSD and hypertension characteristically display increases in circulating
levels of catecholamines, as well as alterations in T-lymphocyte-driven inflammation. T-lymphocytes
are highly reactive to catecholamines, and we have previously reported that splenic T-lymphocytes
exposed to these neurotransmitters in vitro secrete increased levels of interleukin 6 (IL-6) and
interleukin 17A (IL-17A); pro-inflammatory cytokines which have been mechanistically linked to the
pathogenesis of hypertension. Furthermore, using an accepted preclinical mouse model of PTSD
known as repeated social defeat, we have also recently described increased splenic catecholamine
levels, elevated circulating IL-6 and IL-17A levels, as well as a potentiated hypertensive response to
angiotensin II (AngII) in animals undergoing this psychological trauma. These observations were
abrogated in socially-defeated mice lacking T-lymphocytes, demonstrating these adaptive immune
cells are mechanistic in the sensitization to hypertension after trauma. To this end, I hypothesize that
psychological trauma increases the splenic catecholamine milieu that drives T-lymphocyte
inflammation causing hypertension sensitization. In Specific Aim 1, I will determine the contribution of
neuronally-derived catecholamines in the sensitization of hypertension by selectively ablating the
splenic nerve. In Specific Aim 2, I will utilize a novel genetic knockout mouse model that lacks
tyrosine hydroxylase—the rate-limiting enzyme in catecholamine synthesis—exclusively in T-
lymphocytes. I will investigate the contribution of these sources of catecholamines to the A)
behavioral phenotype, B) T-lymphocyte autonomic and inflammatory profiles, and C) development of
hypertension. Completion of these aims will further our ability to design and implement novel
therapies that will ultimately reduce the morbidity and mortality of cardiovascular disease in PTSD
patients.

## Key facts

- **NIH application ID:** 10064671
- **Project number:** 1F30HL154535-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Safwan Kijana Elkhatib
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,403
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064671

## Citation

> US National Institutes of Health, RePORTER application 10064671, Neuroimmune contributions to hypertension sensitization in a preclinical model of PTSD (1F30HL154535-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10064671. Licensed CC0.

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