# Sex disparities in hypoxic sympatholysis and impact of obesity

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $24,212

## Abstract

PROJECT SUMMARY
Parent grant “Sex disparities in hypoxic sympatholysis and impact of obesity” #R01HL153523
Strong evidence implicates the sympathetic nervous system as a key regulator of peripheral blood
flow and blood pressure during hypoxia. Herein, we present striking sex-differences in the
neurovascular response to hypoxia that challenge current dogma. Our results are corroborated
by epidemiological data showing sex disparities in the prevalence of hypertension and
progression of cardiovascular disease in conditions of hypoxemia (i.e., sleep apnea). However,
contributing mechanisms (including α- and β-adrenergic receptor activity, sensitivity, and
expression) remains a critically unanswered question. The present study will fill this gap in
knowledge while also determining whether these mechanisms are impaired with obesity. Nearly
70% of the US population is overweight or obese, with the prevalence of obesity even greater in
patients with sleep apnea. Obese adults exhibit greater sympathetic nervous system activity and
higher risk for hypertension than normal weight adults. Emerging data indicate the impact of
obesity on cardiovascular health is disproportionate in women versus men and it is reasonable to
propose this is exaggerated with the addition of hypoxic stress. The purpose of this application
is to examine key mechanisms contributing to sex-differences in hypoxic vasodilation and the
impact of obesity, with particular emphasis on the sympathetic nervous system. Our central
hypothesis is that young premenopausal, normal weight women are protected from the
sympathetic vasoconstrictor effects of hypoxia, and the “beneficial” effect of female sex is lost
with obesity. Based on strong preliminary data, we anticipate α-adrenergic mediated
vasoconstriction is exaggerated and β-adrenergic and downstream nitric oxide-mediated
vasodilation are attenuated in obese women. We will test our central hypothesis via the following
specific aims: The first aim of this project will determine sex differences in α-adrenergic receptor
mediated vasoconstriction during acute hypoxia as well as the impact of obesity. We propose a
comprehensive approach of intra-arterial drug infusions of α-adrenergic agonists and antagonists,
combined with direct measures of muscle sympathetic nerve activity in normal weight men,
normal weight women, and obese women. The second aim of this project will determine the
direct and modulatory effect of the β-adrenergic receptors on hypoxic vasodilation as well as
impact of obesity. We will collect human arterial endothelial cells and measure the peripheral
vascular response to hypoxia prior to and following intra-arterial infusion of select β-adrenergic
agonists and antagonists. This experimental approach will allow us to strategically assess β-
adrenergic receptor activity, sensitivity, and expression in the context of hypoxia as well as down-
stream mechanisms. Our proposed findings will advance the fundamental, mechanistic
unders...

## Key facts

- **NIH application ID:** 10413582
- **Project number:** 3R01HL153523-02S1
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Jacqueline K Limberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $24,212
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413582

## Citation

> US National Institutes of Health, RePORTER application 10413582, Sex disparities in hypoxic sympatholysis and impact of obesity (3R01HL153523-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10413582. Licensed CC0.

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