Sex Differences in Sympathetic Vascular Reactivity at High Altitude

Not Applicable

Completed

• Conditions: Vasodilation; Vasoconstriction
• Interventions: Drug: Sodium Nitroprusside; Drug: Phenylephrine Hydrochloride; Drug: Norepinephrine; Other: Isometric Handgrip and Post-Exercise Circulatory Occlusion; Other: Rhythmic Handgrip; Other: Cold Pressor Test; Drug: Propranolol Hydrochloride; Drug: Phentolamine Mesylate

• Registration Number: NCT05525416
• Lead Sponsor: University of Alberta

Brief Summary

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

About 200 million people worldwide live at high altitudes and millions of others travel to high altitude every year for work or pleasure. At high altitude participants are exposed to a lower than normal level of oxygen, also known as hypoxia. This causes stress to the human body, which will adapt in order to maintain adequate oxygen delivery to its tissues. One of these adaptations is an increase in activity of participants' sympathetic nervous system ("fight or flight" response). Sympathetic nerve activity affects the size of participants' blood vessels, which in turn will affect blood pressure. Men and women regulate their blood pressure in different ways; for example, women tend to have lower blood pressure and sympathetic nerve activity than men. Women also appear to have less constriction of their blood vessels in response to stress. This may be in part because estrogen causes blood vessels to dilate. It may also be due to differences in the receptors which are activated by the sympathetic nervous system. These receptors are called alpha and beta receptors and respond to sympathetic nerve activity in opposite directions. Women represent 50% of the population living at and travelling to high altitude, therefore, it is important to understand the differences in how men and women respond to low oxygen.

The main purpose of this study is to examine the differences between men and women in the sympathetic nervous system control of blood vessels during exposure to low oxygen. To study this question, the investigators will test how blood vessels respond to stressors in both men and women. Participants will be recruited at the Canadian sites, and the investigators will test them while they breathe low oxygen for a short amount of time at low altitude. The investigators 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.

Study Timeline

• Study First Submitted: 2022-07-22
• Study Start: 2022-07-28
• Study First Submitted QC: 2022-08-30
• Study First Posted: 2022-09-01
• Primary Completion: 2023-02-05
• Study Completion: 2023-02-05
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-22
• Last Update Posted: 2023-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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)
• Participants who are current daily smokers
• Those with a known allergy to sulfites
• Participants taking monoamine oxidase (MAO) inhibitors or tricyclic antidepressants or other medications that have contraindications with the study drugs
• Participants who are still within the washout period from participating in other studies involving drugs.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High Altitude	Propranolol Hydrochloride	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
Low Altitude	Phentolamine Mesylate	Participants will be assessed at an altitude of \<1050m.
Low Altitude	Isometric Handgrip and Post-Exercise Circulatory Occlusion	Participants will be assessed at an altitude of \<1050m.
Low Altitude	Sodium Nitroprusside	Participants will be assessed at an altitude of \<1050m.
Low Altitude	Rhythmic Handgrip	Participants will be assessed at an altitude of \<1050m.
Low Altitude	Propranolol Hydrochloride	Participants will be assessed at an altitude of \<1050m.
High Altitude	Phentolamine Mesylate	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
Low Altitude	Cold Pressor Test	Participants will be assessed at an altitude of \<1050m.
High Altitude	Sodium Nitroprusside	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
High Altitude	Isometric Handgrip and Post-Exercise Circulatory Occlusion	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
High Altitude	Rhythmic Handgrip	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
High Altitude	Cold Pressor Test	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
Low Altitude	Norepinephrine	Participants will be assessed at an altitude of \<1050m.
Low Altitude	Phenylephrine Hydrochloride	Participants will be assessed at an altitude of \<1050m.
High Altitude	Phenylephrine Hydrochloride	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.
High Altitude	Norepinephrine	Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.

Primary Outcome Measures

Name	Time	Method
Change in systolic, diastolic, and mean arterial blood pressure	3 minutes	modified oxford
Propranolol	2 hours	changes in vascular conductance
Change in arterial blood flow	1 hour 30 minutes	phenylephrine and norepinephrine sensitivity
Cold pressor test	3 minutes	sympathetic reactivity
Change in vascular conductance	20 minutes	exercise and metaboreflex reactivity
Phentolamine	1 hour	changes in vascular conductance

Trial Locations

Locations (2)

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

University of British Columbia - Okanagan; 🇨🇦 Kelowna, British Columbia, Canada