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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат Placebo
  Participants will take a placebo sugar pill before and after a bout of prolonged sitting as a control session.
• Препарат Fluconazole 150 mg
  Participants will take 150mg of fluconazole, an EDHF inhibitor before and after a bout of prolonged sitting.

Первичные конечные точки

• Popliteal Low-Flow Mediated Constriction [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting]
• Acute Blood Pressure [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]
• Ambulatory Blood Pressure [Срок оценки: 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.]

Вторичные конечные точки (12)

• Carotid Artery Blood Flow Velocity [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]
• Middle Cerebral Artery Velocity [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]
• Popliteal Flow Mediated Dilation (FMD) [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]
• Physical Activity Behaviour Questionnaire [Срок оценки: At time of study enrolment]
• Heart Rate Variability (HRV) [Срок оценки: 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) [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]
• Carotid Artery Distensibility [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]
• Blood Pressure Varibility (BPV) [Срок оценки: 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) [Срок оценки: Before prolonged sitting, after 1 hour of sitting, after 2-hours of sitting.]
• Habitual Activity [Срок оценки: Before first bout of sitting, after each bout of sitting.]
• Habitual Postures [Срок оценки: Before first bout of sitting, after each bout of sitting.]
• Baseline Arterial Diameters [Срок оценки: Before prolonged sitting, after 1-hour of sitting, after 2-hours of sitting.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Канада · 1 центр

• Dalhousie University — Halifax

Публикации

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• Pellerine LP, Miller K, Frayne RJ, O'Brien MW. Characterizing objective and self-report habitual physical activity and sedentary time in outpatients with an acquired brain injury. Sports Med Health Sci. 2024 Feb 10;6(4):338-343. doi: 10.1016/j.smhs.2024.02.001. eCollection 2024 Dec. PMID 39309460
• Bays HE, Toth PP, Kris-Etherton PM, Abate N, Aronne LJ, Brown WV, Gonzalez-Campoy JM, Jones SR, Kumar R, La Forge R, Samuel VT. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association. J Clin Lipidol. 2013 Jul-Aug;7(4):304-83. doi: 10.1016/j.jacl.2013.04.001. Epub 2013 May 31. PMID 23890517
• O'Brien MW, Johns JA, Al-Hinnawi A, Kimmerly DS. Popliteal flow-mediated dilatory responses to an acute bout of prolonged sitting between earlier and later phases of natural menstrual and oral contraceptive pill cycles. J Appl Physiol (1985). 2020 Oct 1;129(4):637-645. doi: 10.1152/japplphysiol.00424.2020. Epub 2020 Aug 13. PMID 32790597
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• Ishikura F, Beppu S, Hamada T, Khandheria BK, Seward JB, Nehra A. Effects of sildenafil citrate (Viagra) combined with nitrate on the heart. Circulation. 2000 Nov 14;102(20):2516-21. doi: 10.1161/01.cir.102.20.2516. PMID 11076826
• Lopes van Balen VA, van Gansewinkel TAG, de Haas S, van Kuijk SMJ, van Drongelen J, Ghossein-Doha C, Spaanderman MEA. Physiological adaptation of endothelial function to pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017 Dec;50(6):697-708. doi: 10.1002/uog.17431. PMID 28170124
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Идентификаторы

NCT: NCT07396857 · 2025-7915

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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