Sex Disparities in Hypoxic Vasodilation and Impact of Obesity
University of Missouri-Columbia
Summary
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.
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.
Eligibility
- Age range
- 18–45 years
- Sex
- All
- 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
Interventions
- DrugPropranolol Hydrochloride
Regional forearm blockade of β-adrenergic receptors at 20 mcg/dL/min via brachial artery catheter during normoxia and hypoxia exposures
- DrugIsoproterenol
Dose response (1, 3, 6, and 12 ng/dL/min) regional infusion to assess β-adrenergic receptor responsiveness
- DrugPhentolamine 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).
- DrugNorepinephrine
Regional forearm infusion at 8 ng/dL/min via brachial artery catheter during normoxia and hypoxia exposures
Location
- University of MissouriColumbia, Missouri