Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
基本信息
- 批准号:10648023
- 负责人:
- 金额:$ 6.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdrenergic AgentsAdrenergic AntagonistsAdrenergic alpha-AgonistsAdrenergic beta-AgonistsAdultAreaAttenuatedBlood PressureBlood VesselsBlood flowBody mass indexCardiovascular DiseasesCardiovascular systemCatecholaminesChronicCohort StudiesDataDevelopmentDexmedetomidineEndothelial CellsEstrogen Receptor alphaEstrogensExhibitsExposure toFailureFemaleForearmFunctional disorderGoalsHumanHypertensionHypoxemiaHypoxiaImpairmentInfusion proceduresInterventionIntra-Arterial InfusionsIsoproterenolKnowledgeMeasuresMediatingMuscleNerveNeurotransmittersNitric OxideNorepinephrineObesityOverweightOxygenPathogenesisPatientsPeripheralPharmaceutical PreparationsPharmacologyPhentolaminePhenylephrinePhysiologicalPlasmaPopulationPremenopausePrevalencePropranololReceptor ActivationRegulationRelaxationResearchResistanceRiskRisk FactorsRoleSex DifferencesSkeletal MuscleSleep Apnea SyndromesStressSympathetic Nervous SystemTestingVasoconstrictor AgentsVasodilationWeightWomanWorkadult obesityalpha-adrenergic receptorbasebeta-adrenergic receptorblood pressure elevationcardiovascular healthepidemiologic datafallshigh riskimprovedineffective therapiesmenmortalityneurovascularnormoxianovel therapeuticsperipheral bloodpre-clinicalpreservationpreventreceptor sensitivityresponsesexsex disparityvasoconstrictionyoung manyoung woman
项目摘要
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 pathophysiology in sleep apnea and other conditions of hypoxia.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jacqueline K Limberg其他文献
Jacqueline K Limberg的其他文献
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{{ truncateString('Jacqueline K Limberg', 18)}}的其他基金
Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
- 批准号:
10855355 - 财政年份:2020
- 资助金额:
$ 6.26万 - 项目类别:
Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
- 批准号:
10663073 - 财政年份:2020
- 资助金额:
$ 6.26万 - 项目类别:
Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
- 批准号:
10455458 - 财政年份:2020
- 资助金额:
$ 6.26万 - 项目类别:
Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
- 批准号:
10030435 - 财政年份:2020
- 资助金额:
$ 6.26万 - 项目类别:
Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
- 批准号:
10202732 - 财政年份:2020
- 资助金额:
$ 6.26万 - 项目类别:
Sex disparities in hypoxic sympatholysis and impact of obesity
缺氧交感神经的性别差异和肥胖的影响
- 批准号:
10413582 - 财政年份:2020
- 资助金额:
$ 6.26万 - 项目类别:
Reflex responses to intermittent hypoxia in humans: Mechanisms and consequences
人类对间歇性缺氧的反射反应:机制和后果
- 批准号:
9754859 - 财政年份:2016
- 资助金额:
$ 6.26万 - 项目类别:
Reflex responses to intermittent hypoxia in humans: Mechanisms and consequences
人类对间歇性缺氧的反射反应:机制和后果
- 批准号:
9321061 - 财政年份:2016
- 资助金额:
$ 6.26万 - 项目类别:
Reflex responses to intermittent hypoxia in humans: Mechanisms and consequences
人类对间歇性缺氧的反射反应:机制和后果
- 批准号:
9513791 - 财政年份:2016
- 资助金额:
$ 6.26万 - 项目类别:
Insulin-sensing capabilities of the carotid chemoreceptors
颈动脉化学感受器的胰岛素感应能力
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8716913 - 财政年份:2014
- 资助金额:
$ 6.26万 - 项目类别:
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