# Sympathetic neural patterns and transduction in obesity-associated hypertension

> **NIH NIH K99** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $134,352

## Abstract

PROJECT SUMMARY
Cardiovascular mortality attributable to hypertension (HTN) has increased by more than 10 percent in the last
decade, due in part to the escalating obesity epidemic. Effective therapeutic options for HTN are limited and
despite a high prevalence of multi-pharmacological approaches, more than 50% of hypertensive individuals
remain uncontrolled. As such, studies that advance understanding of basic mechanisms of blood pressure
regulation in humans are needed to identify novel therapeutic targets. Exaggerated sympathetic nervous activity
(SNA) and vasoconstriction are hallmark features of many cardiovascular diseases including obesity-associated
HTN (Ob-HTN). Causes of exaggerated sympathetic vasoconstriction are unclear, however recent advances in
quantification of sympathetic activity have uncovered unique action potential patterns that influence the
peripheral vasoconstrictor response to stress. In animal models, sympathetic firing patterns during stress
increase co-release of the potent vasoconstrictor neuropeptide Y (NPY) in conjunction with norepinephrine,
causing a shift in the mechanisms of vasoconstriction towards NPY-mediated signaling. NPY causes
vasoconstriction via activation of NPY 1 receptors (Y1R), and facilitates α-adrenergic mediated signaling causing
exaggerated sympathetic vasoconstriction. We hypothesize that physiological stressors like obesity and hypoxia
alter sympathetic action potential patterns that cause vasoconstriction to rely on NPY-mediated signaling. The
overall aim of this proposal is to 1) identify how sympathetic action potential patterns change in response to
chemoreflex and mental stress 2) to assess the impact of action potential patterns on mechanisms of
vasoconstriction in healthy adults and in patients with Ob-HTN. To accomplish these goals, we will we will assess
beat-by-beat vasoconstriction in response to endogenous bursts of SNA during pharmacological manipulation
of α-adrenergic receptors and Y1Rs to determine the mechanisms of exaggerated sympathetic vasoconstriction
during chemoreflex/mental stress in healthy adults and Ob-HTN patients. We anticipate that these investigations
will 1) further understanding of the basic signaling mechanisms responsible for neurovascular transduction in
humans including the interaction between action potential patterns, neurotransmission and vasoconstriction 2)
identify new mechanisms underlying exaggerated neurovascular transduction in Ob-HTN and 3) provide
avenues for research in other patient populations characterized by elevated SNA and exaggerated
vasoconstriction including sleep apnea, metabolic disease, and heart failure.

## Key facts

- **NIH application ID:** 10247728
- **Project number:** 5K99HL153777-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Christopher M Hearon
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $134,352
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247728

## Citation

> US National Institutes of Health, RePORTER application 10247728, Sympathetic neural patterns and transduction in obesity-associated hypertension (5K99HL153777-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247728. Licensed CC0.

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