Sex Differences in Sympathetic Vascular Reactivity at High Altitude

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.

Conditions

• Vasodilation
• Vasoconstriction

Interventions

DRUG

Sodium Nitroprusside

A bolus injection of sodium nitroprusside will be given to lower blood pressure and evaluate baroreflex function.

DRUG

Phenylephrine Hydrochloride

A bolus injection of phenylephrine will be given to raise blood pressure and evaluate baroreflex function immediately following the sodium nitroprusside infusion.

DRUG

Phenylephrine Hydrochloride

Investigators will give three incremental doses via brachial artery catheter to observe α1-adrenoreceptor mediated vasoconstriction. This will occur three times throughout the protocol.

DRUG

Norepinephrine

Investigators will give three incremental doses via brachial artery catheter to observe adrenoreceptor activation. This will occur three times throughout the protocol.

OTHER

Isometric Handgrip and Post-Exercise Circulatory Occlusion

Participants will perform 2 minutes of isometric handgrip at 30% maximal voluntary contraction followed by 2 minutes of post-exercise circulatory occlusion to assess the reactivity of the blood vessels to exercise and the metaboreflex.

OTHER

Rhythmic Handgrip

Participants will perform 3 minutes of rhythmic handgrip at 25% maximal voluntary contraction to assess the reactivity of blood vessels to dynamic exercise.

OTHER

Cold Pressor Test

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.

DRUG

Propranolol Hydrochloride

Local infusion via brachial artery catheterization will occur continuously for the remainder of the study. Propranolol is a beta-adrenergic antagonist and will allow investigation of the role of beta receptors in responses to various stressors. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion.

DRUG

Phentolamine Mesylate

Local infusion via brachial artery catheterization will occur continuously for the remainder of the study. Phentolamine is an alpha-adrenergic antagonist and will allow investigation the role of alpha receptors in responses to various stressors. It will be continuously infused with propranolol. The above phenylephrine, norepinephrine, isometric handgrip, post-exercise circulatory occlusion, and rhythmic handgrip protocols will be repeated under propranolol infusion.

Sponsors & Collaborators

• University of Alberta

  lead OTHER

Principal Investigators

• Sean van Diepen, MD, MSc · University of Alberta

• Craig D Steinback, PhD · University of Alberta

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-07-28

Primary Completion

2023-02-05

Completion

2023-02-05

Countries

• Canada

Study Locations