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Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences

Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences

Status
Recruiting
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05997732
Acronym
STARS
Enrollment
30
Registered
2023-08-18
Start date
2023-10-31
Completion date
2027-12-01
Last updated
2026-01-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Vasoconstriction, Vasodilation

Keywords

sympathetic nerve activity, sex differences, adrenergic receptors, neurovascular transduction

Brief 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.

Detailed description

Blood pressure is in part regulated by activity of your sympathetic nervous system (also known as your fight or flight response). Sympathetic nerve activity affects the size of your blood vessels, which in turn will affect your blood pressure. This communication between sympathetic impulses and the resulting change in vascular resistance is termed sympathetic neurovascular transduction. In other words, transduction represents the reactivity of the blood vessels in response to individual sympathetic bursts of activity. Males and females regulate their blood pressure in different ways; for example, females tend to have lower blood pressure and sympathetic nerve activity than males. Females also appear to have less constriction of their blood vessels in response to stress. This may be due to differences in the receptors which are activated by the sympathetic nervous system. These receptors are called α and β-adrenergic receptors and are located on vascular smooth muscle cells. They respond to sympathetic neurotransmitters such as norepinephrine in opposite directions: α-adrenoreceptors cause vasoconstriction (and an increase in vascular resistance), and β-adrenoreceptors cause vasodilation (and a decrease in vascular resistance) in part through the endothelium-dependent nitric oxide pathway. Current evidence suggests that β-adrenergic receptors are more sensitive in females and contribute to paradoxical vasodilation when α-adrenergic receptors are stimulated by norepinephrine from sympathetic bursts. It has also been suggested that estrogen interacts with adrenergic receptors, contributing to this sex difference. This study will contribute to the understanding of sex differences in cardiovascular physiology and may have implications for clinical cardiovascular conditions.

Interventions

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

DRUGIsoproterenol Hydrochloride

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

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

DRUGPropranolol Hydrochloride

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

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

Sponsors

University of Alberta
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

Participants will complete three pharmacological conditions, and serve as their own controls.

Eligibility

Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes

Inclusion criteria

* Between ages 18-40 years * No diagnosed medical history of cardiovascular, respiratory, nervous system, or metabolic disease. * Females must be pre-menopausal. * Prior to study visit: abstained from caffeine, alcohol, strenuous exercise, and medication not taken regularly for at least 12 hours.

Exclusion criteria

* Current diagnosis of cardiovascular, respiratory, nervous system, or metabolic disease that may impact blood pressure regulation. This will be assessed on a case-by-case basis by the study physician. * Participants with bleeding or clotting disorders, or those currently taking blood thinners. * Participants currently taking beta-agonist inhalers i.e. Ventolin (at least not in the last 24 hours). * Females who are pregnant, confirmed by a pregnancy test. * Females who have are less than 1 year postpartum or are breastfeeding. * Females who are post-menopausal. * Participants that are classified as obese (body mass index \> 30 kg ⋅ m2). * Have a history of smoking regularly in the last 6 months (but nicotine substitutes (i.e. patch, gum) are not an

Design outcomes

Primary

MeasureTime frameDescription
Circulating sympathetic neurotransmitter concentrations2 minutesBlood sample
Forearm blood flow10 minutes per condition + 2 minutes per agonist dose = 60 minutesMeasured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Forearm vascular resistance10 minutes per condition + 2 minutes per agonist dose = 60 minutesMeasured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Forearm vascular conductance10 minutes per condition + 2 minutes per agonist dose = 60 minutesMeasured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Arterial blood pressure10 minutes per condition + 2 minutes per agonist dose = 60 minutesMeasured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Muscle sympathetic nerve activity10 minutes per condition = 30 minutesResting baseline
Circulating sex hormone concentrations2 minutesBlood samples

Secondary

MeasureTime frameDescription
Arterial-venous blood gas concentrations2 minutes per sample = 6 minutesBlood sample during each condition

Countries

Canada

Contacts

Primary ContactEmily Vanden Berg, MSc
ervanden@ualberta.ca(780)-492-5553
Backup ContactNicholas Cheung, MSc
nkcheung@ualberta.ca(780)-492-5553

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026