The Role of EDHFs on Blood Pressure Following a Bout of Prolonged Sitting

April 7, 2026 updated by: Myles William O'Brien, Université de Sherbrooke

The Role of Endothelial-Derived Hyperpolarization Factors on 24-hr Blood Pressure Regulation Following a Bout of Prolonged Sitting

Canadians spend most of their day in sedentary postures (i.e., sitting, lying, reclining). While the beneficial impacts of physical activity on the heart are well-established, less is known about the consequences during time spent in sedentary postures. Currently, we know that spending time in a bout of uninterrupted sitting disrupts blood pressure regulation. However, it is unknown if there are any 'carry over' effects following uninterrupted sitting bouts (i.e., over the next 24-hours). The release of chemicals from arteries controls how stiff or relaxed they are and is important for controlling blood pressure. This is especially true for arteries directly impacted by sitting (e.g., the popliteal artery behind the knee) and that send blood to the brain (e.g., the carotid artery). We have also established that endothelial-derived hyperpolarizing factors (EDHF, chemicals that relax the artery) are important for the relaxation of the artery the popliteal artery. However, we do not know if the effects of EDHFs on this artery are decreased during or after a bout of uninterrupted sitting. A bout of prolonged sitting also causes blood pressure and fluctuations in blood pressure to increase. Importantly, we reported that fluctuations in blood pressure caused by sitting are higher in young males versus females, but average blood pressure was higher among females. These findings suggest that sitting exerts sex differences in the control of blood pressure. Importantly, these effects were only demonstrated during the 2-hour bout of sitting. As such, it is unknown whether blood pressure is negatively impacted after prolonged sitting. The proposed study will determine the impact of EDHFs on blood pressure regulation following a 2-hour bout of prolonged sitting among a group of healthy males and females. Continuous heart rate (via electrocardiogram) and blood pressure (via finger cuff), as well as blood flow from the common carotid artery (in the neck), middle cerebral artery (in the brain) and popliteal artery (behind the knee) will be measured before and after sitting (via ultrasound). The ability of the popliteal artery to relax will be assessed using ultrasound following the release of a pressure cuff. Finally, 24-hour blood pressure and heart rate will be recorded after sitting using a monitor worn for 24-hours. The role of EDHFs will be investigated by comparing 1) baseline blood flow and blood pressure responses (no sitting), 2) blood pressure responses following a 2-hour bout of sitting, and 3) the blood pressure responses following a 2-hour bout of sitting while suppressing the release of EDHFs (via fluconazole ingestion).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H4R2
        • Recruiting
        • Dalhousie University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Are between the ages of 18-65.
  • Have a body mass index of <40kg/m2 (non-obese).
  • Have not smoked nicotine or marijuana-containing products most days of the week within the past 6 months.
  • Have not been diagnosed with a cardiovascular, cerebrovascular, respiratory, or metabolic disease.
  • Are normotensive.
  • Are not currently taking any medications for cardiovascular, metabolic, pulmonary, or neurological disorders, or taking sildenafil regularly.
  • Are not allergic to the adhesive used to secure the activPAL activity monitors.
  • Are not pregnant or breastfeeding.
  • Are not regularly taking any of the following: another anti-fungal, heartburn medications containing cisapride (e.g., Propulsid), depression medications containing amitriptyline (e.g., Elavil) or nortriptyline (e.g., Pamelor), erythromycin (antibiotic), lipid lower medications (i.e., statins), non-steroidal anti-inflammatory drugs (e.g., ibuprofen), or vitamin A supplements.

Exclusion Criteria:

  • o Younger than 18 years old. Individuals younger than 18 demonstrate more variable peak FMD responses and require multiple assessments to determine peak response.

    • Over the age of 65. There are age-related impacts on arterial function and the responses to sitting.
    • Body mass index of >40 kg/m2 (i.e., obese II category)(6-8).
    • Smoked nicotine or marijuana-containing products most days of the week within the past 6 months. Cardiovascular health for participants who smoke is poor compared to those who do not smoke, which will negatively impact our arterial function outcomes.
    • Have been diagnosed with a cardiovascular, cerebrovascular, respiratory, or metabolic disease. Such conditions impact our assessments of arterial health. The results of unhealthy participants are not of interest in this study.
    • Hypertension (seated resting systolic pressure >139 mmHg and/or diastolic pressure >89 mmHg). Hypertensive individuals have impairments in artery health, which will affect their baseline artery health measures.
    • Hypotensive (seated resting systolic pressure <90 mmHg and/or diastolic pressure <60 mmHg). Hypotensive people are more likely to experience further reductions in blood pressure during the sitting protocol, which will increase the risk of fainting and/or dizziness.
    • Have a history of fainting and/or dizziness during sitting or standing.
    • Prescribed medications for cardiovascular, metabolic, pulmonary, or neurological disorders. This includes people using hormone replacement therapy. These medications will interfere with our assessments and interpretation of arterial health.
    • Have a known allergy to the clear medical adhesive used to secure the activPAL activity monitors.
    • Females who are pregnant or breastfeeding. Pregnant and breastfeeding females are ineligible to participate. This is due to the known increases in arterial vasodilation associated with pregnancy related sex hormones.
    • Currently or recently (within the past 6 months) regularly taking sildenafil or other medications that increase the relaxing effects of nitric oxide in arteries. Such medication will influence artery blood flow and flow-mediated dilation responses.
    • Are regularly taking any of the following: another anti-fungal, heartburn medications containing cisapride (e.g., Propulsid), depression medications containing amitriptyline (e.g., Elavil) or nortriptyline (e.g., Pamelor), erythromycin (antibiotic), lipid lower medications (i.e., statins), non-steroidal anti-inflammatory drugs (e.g., ibuprofen), or vitamin A supplements. These are to minimize the chance of a participant experiencing an adverse reaction to the fluconazole tablet.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Males
Drug: Placebo
Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
Drug: Fluconazole 150 mg
Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.
Experimental: Females
Drug: Placebo
Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
Drug: Fluconazole 150 mg
Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Popliteal Low-Flow Mediated Constriction
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting
During a period of distal cuff-induced ischemia, the endothelial-dependent vasoconstrictor response will be assessed via Duplex ultrasonography. The popliteal artery will be imaged slightly above the popliteal fossa. The L-FMC response will be quantified as the percent reduction in arterial diameter from baseline to the nadir diameter from the last 30-s of a 5-min distal cuff occlusion period.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting
Acute Blood Pressure
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Beat-by-beat systolic (SBP) and diastolic (DBP) blood pressure will be measured using finger photoplethysmography for 20 minutes before the bout of prolonged sitting, 20 minutes after 1-hour of sitting, and 20 minutes after 2-hours of sitting. Mean arterial pressure will be quantified as 1/3 SBP + 2/3 DBP.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Ambulatory Blood Pressure
Time Frame: This will be worn for a 24-hour period before the first prolonged sitting session, and for 24-hours after each bout of prolonged sitting.
Using an ABPMpro Ambulatory Blood Pressure Monitors, habitual blood pressure will be measured every 20-minutes during waking hours, and every 30-minutes during sleeping hours.
This will be worn for a 24-hour period before the first prolonged sitting session, and for 24-hours after each bout of prolonged sitting.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Carotid Artery Blood Flow Velocity
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Blood flow velocity will be measured immediately prior to the bifurcation in the common carotid artery using Duplex ultrasonography for 5 minutes.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Middle Cerebral Artery Velocity
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Blood flow velocity will be measured via transcranial Doppler over the trans-temporal window for 5 minutes.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Popliteal Flow Mediated Dilation (FMD)
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Following a period of distal cuff induced ischemia, the endothelial-dependent vasodilator response will be assessed via Duplex ultrasonography. The popliteal artery will be imaged slightly above the popliteal fossa. The FMD response will be quantified as the percent increase in arterial diameter from baseline to the peak diameter following the release of the distal cuff.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Physical Activity Behaviour Questionnaire
Time Frame: At time of study enrolment
A subjective questionnaire that provides information regarding habitual physical activity and sedentary behaviours.
At time of study enrolment
Heart Rate Variability (HRV)
Time Frame: Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Heart rate will be determined using cardiac intervals from a lead II electrocardiography during prolonged sitting, and from the built-in electrocardiogram in the ambulatory blood pressure monitor. HRV will be derived from these waveforms using an offline HRV analysis module. Time-domain (I.e., RMSSD), frequency-domain, low frequency (LF) power, high frequency (HF) power, and the LF/HF ratio will be quantified for each participant.
Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Carotid Intima Media Thickness (cIMT)
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
cIMT will be determined from a 5-minute recording of the carotid artery, imaged prior to the bifurcation using Duplex ultrasonography.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Carotid Artery Distensibility
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Distensibility will be determined from 5-minutes of recorded carotid artery imaging via Duplex ultrasonography, and will be calculated as the difference between average arterial diameter during systole and diastole.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Blood Pressure Varibility (BPV)
Time Frame: Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Beat-by-beat BPV during sitting will be quantified using the blood pressure measurements derived from finger photoplethysmography. This will be calculated as the average absolute difference between successive finger blood pressure measurements, for systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Ambulatory BPV will be quantified from the 24-hour blood pressure monitors.
Acute: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting. Ambulatory: 24-hours at baseline, 24-hours after each bout of prolonged sitting.
Cardiovagal Baroreflex Sensitivity (cvBRS)
Time Frame: Before prolonged sitting, after 1 hour of sitting, after 2-hours of sitting.
cvBRS will be quantified from beat-by-beat systolic blood pressure (SBP) and R-R intervals in a cvBRS software. cvBRS outcomes will be quantified from a minimum of 3 sequences in which beat-by-beat SBP changes were ≥1 mmHg and changes in R-R interval were ≥ 1 ms. Overall cvBRS is represented by the average slope of SBP and R-R interval regressions for the pooled sequences, and reported separately for both up and down sequences. Baroreflex effectiveness index (BEI) will be measured as the ratio of the number of SBP ramp-induced changes in RR interval to the total number of SBP ramps observed. This will be reported separately for both up and down sequences. This will be measured over a 20-minute time period.
Before prolonged sitting, after 1 hour of sitting, after 2-hours of sitting.
Baseline Arterial Diameters
Time Frame: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Arterial diameter of the popliteal and carotid arteries will be determined via Duplex ultrasonography over a minimum of 2-minutes.
Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.
Habitual Activity
Time Frame: Before first bout of sitting, after each bout of sitting.
Habitual activity will be measured using activPAL inclinometer-accelerometers positioned on the torso, thigh, and calf. Monitors will be waterproofed and attached 24-hr/day for 8 days via clear medical adhesive. Physical activity will be determined via validated, custom software that was developed and openly published by our group.
Before first bout of sitting, after each bout of sitting.
Habitual Postures
Time Frame: Before first bout of sitting, after each bout of sitting.
Habitual postures will be measured using activPAL inclinometer-accelerometers positioned on the torso, thigh, and calf. Monitors will be waterproofed and attached 24-hr/day for 8 days via clear medical adhesive. Time spent in postures (e.g., sitting versus lying time) will be determined via validated, custom software that was developed and openly published by our group.
Before first bout of sitting, after each bout of sitting.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Université de Sherbrooke

Collaborators

Dalhousie University

Investigators

  • Principal Investigator: Myles W O'Brien, PhD, Université de Sherbrooke

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2025

Primary Completion (Estimated)

December 15, 2026

Study Completion (Estimated)

December 15, 2026

Study Registration Dates

First Submitted

February 2, 2026

First Submitted That Met QC Criteria

February 2, 2026

First Posted (Actual)

February 9, 2026

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-7915

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD will not be shared to maintain privacy and confidentiality of the participants.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cardiovascular

Clinical Trials on Placebo

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe