Sex Differences in Sympathetic Activity and Vascular Reactivity During Acute and Chronic Hypoxia.

Study Overview
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Brief Summary
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This study aims to investigate sex differences in blood pressure control associated with exposure to acute hypoxia (low oxygen), and short term acclimatization to hypoxia at high altitude.

Detailed Description
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About 200 million people worldwide live at high altitudes. Millions of others travel to high altitude every year for work or travel. The low oxygen (or hypoxia) experienced at high altitudes causes considerable physiological stress, and the body adapts in order to maintain adequate oxygen delivery to its tissues. One of these adaptations is an increase in the activity of the sympathetic nervous system. This system is responsible for the fight or flight response. Sympathetic activity regulates the size of the blood vessels, which will affect blood pressure. Previous studies suggest that males and females regulate their blood pressure in different ways. Females tend to have lower resting sympathetic activity, and less vasoconstriction in response to stressors than males. Blood pressure changes are also influenced by levels of sex hormones; for example, estrogen may cause opposing vasodilation. Therefore, it is important to understand the differences in how males and females respond to low oxygen. The main purpose of this study is to examine the differences between males and females in control of blood vessels during exposure to low oxygen. To study this question, we will test vasoreactivity to set physiological stressors in both males and females. Participants will be recruited at the Canadian sites, and we will test them while they breathe low oxygen for a short amount of time at low altitude. We will also perform assessments on the same participants during a two week stay at high altitude at White Mountain, CA, which is at an altitude of 3,800m. These data will have implications in the basic understanding of differences between male and female physiology. Specifically, to males and females living or travelling to high altitude.

Official Title
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Sex Differences in Sympathetic Activity and Vascular Reactivity During Acute and Chronic Hypoxia.

Conditions
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Vasodilation, Vasoconstriction

Intervention / Treatment
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* Drug: Phenylephrine Hydrochloride
* Other: Cold Pressor Test
* Other: Isocapnic Acute Hypoxia
* Other: Hyperoxia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between ages of 18-50 No medical history of cardiovascular, respiratory, nervous system, or metabolic disease Females must be pre-menopausal Exclusion Criteria: Any known cardiovascular, respiratory, nervous system, or metabolic disease (however, participants with controlled arterial hypertension will not be excluded) Having travelled above 2,000m within 1 month of testing at low and high altitude Females who are pregnant, confirmed by a pregnancy test Females who are post-menopausal Participants that are classified as obese (body mass index > 30kg⋅m²) Have a history of smoking regularly in the last 6 months (but nicotine substitutes (patch, gum) not an exclusion criteria) Those with a known allergy to sulfites Participants taking monoamine oxidase (MAO) inhibitors or tricyclic antidepressants

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will partake in all three arms of the study, which include: 1) low altitude, 2) early acclimatization, and 3) late acclimatization to high altitude assessments.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Altitude<br>Participants will be assessed at an altitude of <1050m. | Drug: Phenylephrine Hydrochloride<br>* Series of three incremental bolus injections to observe α1-adrenoreceptor mediated vasoconstriction.<br>* Other names: Neo-Synephrine;Other: Cold Pressor Test<br>* Standardized sympathetic stressor involving submersion of the hand in ice-cold water for 3-minutes, aiming to elicit endogenous neurotransmitter release and blood pressure increases.<br>Other: Isocapnic Acute Hypoxia<br>* During low altitude assessment, participants will be exposed to isocapnic hypoxia equivalent to 3,800m to assess responses to acute exposure.<br>|
| Experimental: Early Acclimatization to High Altitude<br>Participants will be assessed on day 2 or 3 of a high-altitude expedition at 3,800m. | Drug: Phenylephrine Hydrochloride<br>* Series of three incremental bolus injections to observe α1-adrenoreceptor mediated vasoconstriction.<br>* Other names: Neo-Synephrine;Other: Cold Pressor Test<br>* Standardized sympathetic stressor involving submersion of the hand in ice-cold water for 3-minutes, aiming to elicit endogenous neurotransmitter release and blood pressure increases.<br>Other: Hyperoxia<br>* During high altitude assessments, participants will breathe an oxygen concentration comparable to their end-tidal values at low altitude for the assessment of the influences of acclimatization.<br>|
| Experimental: Late Acclimatization to High Altitude<br>Participants will be assessed on day 9 or 10 of a high-altitude expedition at 3,800m. | Drug: Phenylephrine Hydrochloride<br>* Series of three incremental bolus injections to observe α1-adrenoreceptor mediated vasoconstriction.<br>* Other names: Neo-Synephrine;Other: Cold Pressor Test<br>* Standardized sympathetic stressor involving submersion of the hand in ice-cold water for 3-minutes, aiming to elicit endogenous neurotransmitter release and blood pressure increases.<br>Other: Hyperoxia<br>* During high altitude assessments, participants will breathe an oxygen concentration comparable to their end-tidal values at low altitude for the assessment of the influences of acclimatization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | Phenylephrine sensitivity | 18 minutes | 
| Change in arterial blood flow | Phenylephrine sensitivity | 18 minutes | 
| Cold pressor test reactivity |  | 4 minutes |