# Sex disparities in hypoxic sympatholysis and impact of obesity

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $424,570

## Abstract

PROJECT SUMMARY
Strong evidence implicates the sympathetic nervous system as a key regulator of peripheral vascular tone 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 remain 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 during hypoxia 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 the 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 understanding of hypoxic
vascular control in women, and results will ultimately guide the development of new strategies to treat and
prevent vascular pathop...

## Key facts

- **NIH application ID:** 10030435
- **Project number:** 1R01HL153523-01
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Jacqueline K Limberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $424,570
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10030435

## Citation

> US National Institutes of Health, RePORTER application 10030435, Sex disparities in hypoxic sympatholysis and impact of obesity (1R01HL153523-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10030435. Licensed CC0.

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