About this trial
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).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Crossover
Treatments tested in this trial
Placebo
DrugParticipants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
Fluconazole 150 mg
DrugParticipants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.
Treatment groups
Trial outcomes
Primary outcomes
Popliteal Low-Flow Mediated Constriction
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.
Acute Blood Pressure
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.
Ambulatory Blood Pressure
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.
Secondary outcomes
Carotid Artery Blood Flow Velocity
Blood flow velocity will be measured immediately prior to the bifurcation in the common carotid artery using Duplex ultrasonography for 5 minutes.
Middle Cerebral Artery Velocity
Blood flow velocity will be measured via transcranial Doppler over the trans-temporal window for 5 minutes.
Popliteal Flow Mediated Dilation (FMD)
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.
Physical Activity Behaviour Questionnaire
A subjective questionnaire that provides information regarding habitual physical activity and sedentary behaviours.
Sponsors and contacts
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Université de Sherbrooke
Lead sponsor
Dalhousie University
Collaborator