Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

Study Overview
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Brief Summary
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The purpose of this project 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.

Detailed Description
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Patients with sleep apnea are at increased risk of developing cardiovascular disease - with women at potentially greater risk than men. Contributing mechanisms are not well understood, but may be related to how women respond to low oxygen and, given over 70% of patients with sleep apnea are obese, the impact of obesity. This project seeks to increase our understanding of mechanisms that may contribute to sex differences in the cardiovascular response to low oxygen with the hope that this knowledge will improve the efficacy of current therapies and support the discovery of novel therapeutics.

Official Title
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Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

Conditions
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Obesity, Vasodilation, Healthy

Intervention / Treatment
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* Drug: Propranolol Hydrochloride
* Drug: Isoproterenol
* Drug: Phentolamine Mesylate
* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy weight (BMI >18 and <25 kg/m2) Obese (BMI ≥30 kg/m2) Exclusion Criteria: Pregnancy, breastfeeding Diagnosed sleep apnea or AHI >10 events/hr Current smoking/Nicotine use Increased risk of bleeding, pro-coagulant disorders, clotting disorders, anticoagulation therapy Nerve/neurologic disease Cardiovascular, hepatic, renal, respiratory disease Blood pressure ≥140/90 mmHg Diabetes, Polycystic ovarian syndrome Communication barriers Prescription medications, Sensitivity to lidocaine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Hypoxia Exposure<br>Men and women will be exposed to isocapnic hypoxia. Participants will wear a mask and systemic oxygen levels will be titrated to attain hypoxemia as assessed by pulse oximetry. | Drug: Propranolol Hydrochloride<br>* Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures<br>Drug: Isoproterenol<br>* Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness<br>Drug: Phentolamine Mesylate<br>* This infusion will be for 10 min before baseline measurement (12 mcg/dL/min) and continue the infusion at a maintenance rate (5 mcg/dL/min).<br>Drug: Norepinephrine<br>* Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forearm vascular conductance with intra-arterial drug infusion | Vascular conductance is an index of vascular tone and is measured using a technique called venous occlusion plethysmography. | Change from baseline to last 1-minute of drug infusion |