Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-40
SponsorUniversity of Alberta
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Crossover
Treatments tested in this trial
Phenylephrine Hydrochloride
DrugParticipants will receive three incremental doses via the brachial artery catheter to assess α1-adrenoreceptor mediated vasoconstriction.
Isoproterenol Hydrochloride
DrugParticipants will receive four incremental doses via the brachial artery catheter to assess β-adrenoreceptor mediated vasodilation.
Norepinephrine Bitartrate
DrugParticipants will receive three incremental doses via the brachial artery catheter to assess nonspecific adrenoreceptor activation.
Propranolol Hydrochloride
DrugPropranolol will be continuously infused through the brachial artery catheter to induce β-adrenergic blockade locally in the forearm.
Phentolamine Mesylate
DrugPhentolamine will be continuously infused through the brachial artery catheter to induce α-adrenergic blockade locally in the forearm.
Phenylephrine Hydrochloride
DrugParticipants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the α-adrenergic blockade.
Isoproterenol Hydrochloride
DrugParticipants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the β-adrenergic blockade.
Propranolol Hydrochloride
DrugPropranolol will be continuously co-infused with phentolamine to maintain the β-adrenergic blockade.
Treatment groups
30 Participants
are divided into 3 treatment groupsGroup A: Control ConditionExperimental treatment 3 interventions
Group B: β-Adrenergic BlockadeExperimental treatment 2 interventions
Group C: α+β-Adrenergic BlockadeExperimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
Forearm blood flow
Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Time frame
10 minutes per condition + 2 minutes per agonist dose = 60 minutes2
Forearm vascular resistance
Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Time frame
10 minutes per condition + 2 minutes per agonist dose = 60 minutes3
Forearm vascular conductance
Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Time frame
10 minutes per condition + 2 minutes per agonist dose = 60 minutes4
Arterial blood pressure
Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
Time frame
10 minutes per condition + 2 minutes per agonist dose = 60 minutesSecondary outcomes
1
Arterial-venous blood gas concentrations
Blood sample during each condition
Time frame
2 minutes per sample = 6 minutesSponsors and contacts
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Source ClinicalTrials.gov