Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences

Summary

The main purpose of this interventional study is to examine differences in resting blood pressure control between healthy males and females. The main questions it aims to answer are:

1. Are there sex differences in the communication between the sympathetic nervous system (also known as the "fight or flight" response) and peripheral blood vessels (which influence systemic blood pressure)?
2. What is the role of specific vascular receptors that respond to sympathetic signals, and is it different between males and females?

Participants will complete one study visit of approximately 3 hours where they will:

* Have a blood sample taken to measure circulating sex hormone and sympathetic transmitters.
* Receive very small doses of medications commonly used to adjust blood pressure through an artery in their arm. The effects of these medications will be short-acting and localized to the forearm.
* Have their sympathetic nervous activity directly measured through two very small needles (similar to acupuncture needles) in the side of their leg.
* Have their blood pressure and heart rate recorded, and forearm blood flow measured using ultrasound.

Conditions

• Vasoconstriction
• Vasodilation

Interventions

DRUG

Phenylephrine Hydrochloride

Participants will receive three incremental doses via the brachial artery catheter to assess α1-adrenoreceptor mediated vasoconstriction.

DRUG

Isoproterenol Hydrochloride

Participants will receive four incremental doses via the brachial artery catheter to assess β-adrenoreceptor mediated vasodilation.

DRUG

Norepinephrine Bitartrate

Participants will receive three incremental doses via the brachial artery catheter to assess nonspecific adrenoreceptor activation.

DRUG

Propranolol Hydrochloride

Propranolol will be continuously infused through the brachial artery catheter to induce β-adrenergic blockade locally in the forearm.

DRUG

Phentolamine Mesylate

Phentolamine will be continuously infused through the brachial artery catheter to induce α-adrenergic blockade locally in the forearm.

DRUG

Phenylephrine Hydrochloride

Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the α-adrenergic blockade.

DRUG

Isoproterenol Hydrochloride

Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the β-adrenergic blockade.

DRUG

Propranolol Hydrochloride

Propranolol will be continuously co-infused with phentolamine to maintain the β-adrenergic blockade.

Sponsors & Collaborators

• University of Alberta

  lead OTHER

Principal Investigators

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

• Craig Steinback, PhD · University of Alberta

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-10-31

Primary Completion

2027-12-01

Completion

2027-12-01

Countries

• Canada

Study Locations