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临床试验/NCT05997732
NCT05997732招募中4 期

Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences

University of Alberta2 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2023年10月31日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
状态
招募中
入组人数
30
试验地点
2
主要终点
Arterial blood pressure

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Crossover
主要目的
Basic Science
盲法
None

入排标准

年龄范围
18 Years 至 40 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • 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.

排除标准

  • 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).
  • Have a history of smoking regularly in the last 6 months (but nicotine substitutes (i.e. patch, gum) are not an exclusion criteria).
  • 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.

研究组 & 干预措施

Control Condition

Experimental

Normal saline will be infused through the brachial artery catheter at the same calculated rate as propranolol + phentolamine in the α+β-blockade condition to control for volumetric effects.

干预措施: Phenylephrine Hydrochloride (Drug)

Control Condition

Experimental

Normal saline will be infused through the brachial artery catheter at the same calculated rate as propranolol + phentolamine in the α+β-blockade condition to control for volumetric effects.

干预措施: Isoproterenol Hydrochloride (Drug)

Control Condition

Experimental

Normal saline will be infused through the brachial artery catheter at the same calculated rate as propranolol + phentolamine in the α+β-blockade condition to control for volumetric effects.

干预措施: Norepinephrine Bitartrate (Drug)

β-Adrenergic Blockade

Experimental

β-adrenoreceptors will be blocked locally in the forearm using propranolol. Normal saline will be co-infused at the calculated rate of phentolamine in the α+β-blockade condition to control for volumetric effects.

干预措施: Norepinephrine Bitartrate (Drug)

β-Adrenergic Blockade

Experimental

β-adrenoreceptors will be blocked locally in the forearm using propranolol. Normal saline will be co-infused at the calculated rate of phentolamine in the α+β-blockade condition to control for volumetric effects.

干预措施: Propranolol Hydrochloride (Drug)

α+β-Adrenergic Blockade

Experimental

α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.

干预措施: Phentolamine Mesylate (Drug)

α+β-Adrenergic Blockade

Experimental

α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.

干预措施: Phenylephrine Hydrochloride (Drug)

α+β-Adrenergic Blockade

Experimental

α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.

干预措施: Isoproterenol Hydrochloride (Drug)

α+β-Adrenergic Blockade

Experimental

α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.

干预措施: Propranolol Hydrochloride (Drug)

结局指标

主要结局

Arterial blood pressure

时间窗: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes

Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.

Circulating sympathetic neurotransmitter concentrations

时间窗: 2 minutes

Blood sample

Forearm vascular resistance

时间窗: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes

Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.

Forearm vascular conductance

时间窗: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes

Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.

Circulating sex hormone concentrations

时间窗: 2 minutes

Blood samples

Forearm blood flow

时间窗: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes

Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.

Muscle sympathetic nerve activity

时间窗: 10 minutes per condition = 30 minutes

Resting baseline

次要结局

  • Arterial-venous blood gas concentrations(2 minutes per sample = 6 minutes)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (2)

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