NCT05997732

Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: University of Alberta · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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.

Conditions

• Vasoconstriction
• Vasodilation

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2023-10-31
• Primary completion: 2027-12-01
• Completion: 2027-12-01
• First posted: 2023-08-18
• Last updated: 2026-01-08

Locations

1 site across 1 country: Canada