Sex Disparities in Hypoxic Vasodilation and Impact of Obesity

Purpose

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.

Conditions

  • Obesity
  • Vasodilation
  • Healthy

Eligibility

Eligible Ages
Between 18 Years and 45 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • BMI >18 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

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
Hypoxia Exposure 		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
    Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures
  • Drug: Isoproterenol
    Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness
  • Drug: Phentolamine Mesylate
    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).
  • Drug: Norepinephrine
    Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures

Recruiting Locations

University of Missouri
Columbia 4381982, Missouri 4398678 65211
Contact:
Jennifer L Harper
5738822544
harperjl@missouri.edu

More Details

Status
Recruiting
Sponsor
University of Missouri-Columbia

Study Contact

Jacqueline K Limberg, Ph.D.
5738822544
limbergj@missouri.edu

Detailed Description

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.