RecruitingPhase 4NCT05997732

Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences


Sponsor

University of Alberta

Enrollment

30 participants

Start Date

Oct 31, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 40 Years

Inclusion Criteria4

  • 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 Criteria10

  • 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).
  • Those with a known allergy to sulfites, or other components of the supplied solution of study drugs.
  • Participants taking medications that are contraindicated with any of the study drugs, such as monoamine oxidase (MAO) inhibitors or tricyclic antidepressants.
  • Participants who have not adhered to the pre-testing guidelines related to diet, alcohol or exercise will not be excluded, but will be rescheduled for a different day. This is to reduce experimental variability.

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Interventions

DRUGPhenylephrine Hydrochloride

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.

DRUGNorepinephrine Bitartrate

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.

DRUGPhentolamine Mesylate

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

DRUGPhenylephrine Hydrochloride

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

DRUGIsoproterenol Hydrochloride

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

DRUGPropranolol Hydrochloride

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


Locations(1)

University of Alberta

Edmonton, Alberta, Canada

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NCT05997732


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