Sex Differences in Sympathetic Vascular Reactivity at High Altitude

NCT05525416 | Completed

• 1 other identifier: Pro00096808
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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.

Conditions

Vasodilation; Vasoconstriction

Outcome Measures

Primary Outcomes (6)

• Change in systolic, diastolic, and mean arterial blood pressure

  modified oxford

  3 minutes

• Change in arterial blood flow

  phenylephrine and norepinephrine sensitivity

  1 hour 30 minutes

• Change in vascular conductance

  exercise and metaboreflex reactivity

  20 minutes

• Cold pressor test

  sympathetic reactivity

  3 minutes

• Propranolol

  changes in vascular conductance

  2 hours

• Phentolamine

  changes in vascular conductance

  1 hour

Study Arms (2)

Low Altitude

EXPERIMENTAL

Participants will be assessed at an altitude of \<1050m.

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

High Altitude

EXPERIMENTAL

Participants will be assessed on a high-altitude expedition at an elevation of 3,800m.

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

Interventions

Sodium Nitroprusside DRUG

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

High Altitude; Low Altitude

Phenylephrine Hydrochloride DRUG

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

Also known as: Neo-Synephrine

High Altitude; Low Altitude

Norepinephrine DRUG

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

High Altitude; Low Altitude

Isometric Handgrip and Post-Exercise Circulatory Occlusion OTHER

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.

High Altitude; Low Altitude

Rhythmic Handgrip OTHER

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

High Altitude; Low Altitude

Cold Pressor Test OTHER

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.

High Altitude; Low Altitude

Propranolol Hydrochloride DRUG

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.

High Altitude; Low Altitude

Phentolamine Mesylate DRUG

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.

High Altitude; Low Altitude

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between ages of 18-50
• No medical history of cardiovascular, respiratory, nervous system, or metabolic disease
• Females must be pre-menopausal

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (2)

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

Location

University of British Columbia - Okanagan

Kelowna, British Columbia, V1V 1V7, Canada

Location

Related Publications (4)

• Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach JH, Joyner MJ. Sex differences in sympathetic neural-hemodynamic balance: implications for human blood pressure regulation. Hypertension. 2009 Mar;53(3):571-6. doi: 10.1161/HYPERTENSIONAHA.108.126391. Epub 2009 Jan 26.

  PMID: 19171792 BACKGROUND

• Mazzeo RS, Child A, Butterfield GE, Mawson JT, Zamudio S, Moore LG. Catecholamine response during 12 days of high-altitude exposure (4, 300 m) in women. J Appl Physiol (1985). 1998 Apr;84(4):1151-7. doi: 10.1152/jappl.1998.84.4.1151.

  PMID: 9516178 BACKGROUND

• Purdy GM, James MA, Rees JL, Ondrus P, Keess JL, Day TA, Steinback CD. Spleen reactivity during incremental ascent to altitude. J Appl Physiol (1985). 2019 Jan 1;126(1):152-159. doi: 10.1152/japplphysiol.00753.2018. Epub 2018 Nov 21.

  PMID: 30462566 BACKGROUND

• Usselman CW, Gimon TI, Nielson CA, Luchyshyn TA, Coverdale NS, Van Uum SH, Shoemaker JK. Menstrual cycle and sex effects on sympathetic responses to acute chemoreflex stress. Am J Physiol Heart Circ Physiol. 2015 Mar 15;308(6):H664-71. doi: 10.1152/ajpheart.00345.2014. Epub 2014 Dec 19.

  PMID: 25527774 BACKGROUND

MeSH Terms

Conditions

Aneurysm

Interventions

Nitroprusside; Phenylephrine; Norepinephrine; Propranolol; Phentolamine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenoxypropanolamines; Propanolamines; Propanols; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sean van Diepen, MD, MSc

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Craig D Steinback, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Due to the study design, masking is not possible. The time points and dosages of the study drug will be known to the participant.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will partake in both arms of the study, which include: 1) low altitude and 2) high altitude assessments.

Study Record Dates

• First Submitted: July 22, 2022
• First Posted: September 1, 2022
• Study Start: July 28, 2022
• Primary Completion: February 5, 2023
• Study Completion: February 5, 2023
• Last Updated: September 19, 2024

Record last verified: 2023-03

Locations

CA (2)