xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05997732</url>
    </required_header>
    <id_info>
      <org_study_id>Pro00126600</org_study_id>
      <nct_id>NCT05997732</nct_id>
    </id_info>
    <brief_title>Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences</brief_title>
    <acronym>STARS</acronym>
    <official_title>Sympathetic Neurovascular Transduction: Role of Adrenergic Receptors and Sex Differences</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Alberta</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Alberta</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The main purpose of this interventional study is to examine differences in resting blood&#xD;
        pressure control between healthy males and females. The main questions it aims to answer are:&#xD;
  &#xD;
          1. Are there sex differences in the communication between the sympathetic nervous system&#xD;
             (also known as the &quot;fight or flight&quot; response) and peripheral blood vessels (which&#xD;
             influence systemic blood pressure)?&#xD;
  &#xD;
          2. What is the role of specific vascular receptors that respond to sympathetic signals, and&#xD;
             is it different between males and females?&#xD;
  &#xD;
        Participants will complete one study visit of approximately 3 hours where they will:&#xD;
  &#xD;
          -  Have a blood sample taken to measure circulating sex hormone and sympathetic&#xD;
             transmitters.&#xD;
  &#xD;
          -  Receive very small doses of medications commonly used to adjust blood pressure through&#xD;
             an artery in their arm. The effects of these medications will be short-acting and&#xD;
             localized to the forearm.&#xD;
  &#xD;
          -  Have their sympathetic nervous activity directly measured through two very small needles&#xD;
             (similar to acupuncture needles) in the side of their leg.&#xD;
  &#xD;
          -  Have their blood pressure and heart rate recorded, and forearm blood flow measured using&#xD;
             ultrasound.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Blood pressure is in part regulated by activity of your sympathetic nervous system (also&#xD;
        known as your &quot;fight or flight&quot; response). Sympathetic nerve activity affects the size of&#xD;
        your blood vessels, which in turn will affect your blood pressure. This communication between&#xD;
        sympathetic impulses and the resulting change in vascular resistance is termed &quot;sympathetic&#xD;
        neurovascular transduction&quot;. In other words, transduction represents the reactivity of the&#xD;
        blood vessels in response to individual sympathetic bursts of activity.&#xD;
  &#xD;
        Males and females regulate their blood pressure in different ways; for example, females tend&#xD;
        to have lower blood pressure and sympathetic nerve activity than males. Females also appear&#xD;
        to have less constriction of their blood vessels in response to stress. This may be due to&#xD;
        differences in the receptors which are activated by the sympathetic nervous system. These&#xD;
        receptors are called α and β-adrenergic receptors and are located on vascular smooth muscle&#xD;
        cells. They respond to sympathetic neurotransmitters such as norepinephrine in opposite&#xD;
        directions: α-adrenoreceptors cause vasoconstriction (and an increase in vascular&#xD;
        resistance), and β-adrenoreceptors cause vasodilation (and a decrease in vascular resistance)&#xD;
        in part through the endothelium-dependent nitric oxide pathway.&#xD;
  &#xD;
        Current evidence suggests that β-adrenergic receptors are more sensitive in females and&#xD;
        contribute to paradoxical vasodilation when α-adrenergic receptors are stimulated by&#xD;
        norepinephrine from sympathetic bursts. It has also been suggested that estrogen interacts&#xD;
        with adrenergic receptors, contributing to this sex difference. This study will contribute to&#xD;
        the understanding of sex differences in cardiovascular physiology and may have implications&#xD;
        for clinical cardiovascular conditions.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2024</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Participants will complete three pharmacological conditions, and serve as their own controls.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Forearm blood flow</measure>
      <time_frame>10 minutes per condition + 2 minutes per agonist dose = 60 minutes</time_frame>
      <description>Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Forearm vascular resistance</measure>
      <time_frame>10 minutes per condition + 2 minutes per agonist dose = 60 minutes</time_frame>
      <description>Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Forearm vascular conductance</measure>
      <time_frame>10 minutes per condition + 2 minutes per agonist dose = 60 minutes</time_frame>
      <description>Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Arterial blood pressure</measure>
      <time_frame>10 minutes per condition + 2 minutes per agonist dose = 60 minutes</time_frame>
      <description>Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Muscle sympathetic nerve activity</measure>
      <time_frame>10 minutes per condition = 30 minutes</time_frame>
      <description>Resting baseline</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Circulating sex hormone concentrations</measure>
      <time_frame>2 minutes</time_frame>
      <description>Blood samples</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Circulating sympathetic neurotransmitter concentrations</measure>
      <time_frame>2 minutes</time_frame>
      <description>Blood sample</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Arterial-venous blood gas concentrations</measure>
      <time_frame>2 minutes per sample = 6 minutes</time_frame>
      <description>Blood sample during each condition</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Vasoconstriction</condition>
    <condition>Vasodilation</condition>
    <arm_group>
      <arm_group_label>Control Condition</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>β-Adrenergic Blockade</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>α+β-Adrenergic Blockade</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Phenylephrine Hydrochloride</intervention_name>
      <description>Participants will receive three incremental doses via the brachial artery catheter to assess α1-adrenoreceptor mediated vasoconstriction.</description>
      <arm_group_label>Control Condition</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Isoproterenol Hydrochloride</intervention_name>
      <description>Participants will receive four incremental doses via the brachial artery catheter to assess β-adrenoreceptor mediated vasodilation.</description>
      <arm_group_label>Control Condition</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Norepinephrine Bitartrate</intervention_name>
      <description>Participants will receive three incremental doses via the brachial artery catheter to assess nonspecific adrenoreceptor activation.</description>
      <arm_group_label>Control Condition</arm_group_label>
      <arm_group_label>β-Adrenergic Blockade</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propranolol Hydrochloride</intervention_name>
      <description>Propranolol will be continuously infused through the brachial artery catheter to induce β-adrenergic blockade locally in the forearm.</description>
      <arm_group_label>β-Adrenergic Blockade</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Phentolamine Mesylate</intervention_name>
      <description>Phentolamine will be continuously infused through the brachial artery catheter to induce α-adrenergic blockade locally in the forearm.</description>
      <arm_group_label>α+β-Adrenergic Blockade</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Phenylephrine Hydrochloride</intervention_name>
      <description>Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the α-adrenergic blockade.</description>
      <arm_group_label>α+β-Adrenergic Blockade</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Isoproterenol Hydrochloride</intervention_name>
      <description>Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the β-adrenergic blockade.</description>
      <arm_group_label>α+β-Adrenergic Blockade</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Propranolol Hydrochloride</intervention_name>
      <description>Propranolol will be continuously co-infused with phentolamine to maintain the β-adrenergic blockade.</description>
      <arm_group_label>α+β-Adrenergic Blockade</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Between ages 18-40 years&#xD;
  &#xD;
            -  No diagnosed medical history of cardiovascular, respiratory, nervous system, or&#xD;
               metabolic disease.&#xD;
  &#xD;
            -  Females must be pre-menopausal.&#xD;
  &#xD;
            -  Prior to study visit: abstained from caffeine, alcohol, strenuous exercise, and&#xD;
               medication not taken regularly for at least 12 hours.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current diagnosis of cardiovascular, respiratory, nervous system, or metabolic disease&#xD;
               that may impact blood pressure regulation. This will be assessed on a case-by-case&#xD;
               basis by the study physician.&#xD;
  &#xD;
            -  Participants with bleeding or clotting disorders, or those currently taking blood&#xD;
               thinners.&#xD;
  &#xD;
            -  Participants currently taking beta-agonist inhalers i.e. Ventolin (at least not in the&#xD;
               last 24 hours).&#xD;
  &#xD;
            -  Females who are pregnant, confirmed by a pregnancy test.&#xD;
  &#xD;
            -  Females who have are less than 1 year postpartum or are breastfeeding.&#xD;
  &#xD;
            -  Females who are post-menopausal.&#xD;
  &#xD;
            -  Participants that are classified as obese (body mass index &gt; 30 kg ⋅ m2).&#xD;
  &#xD;
            -  Have a history of smoking regularly in the last 6 months (but nicotine substitutes&#xD;
               (i.e. patch, gum) are not an exclusion criteria).&#xD;
  &#xD;
            -  Those with a known allergy to sulfites, or other components of the supplied solution&#xD;
               of study drugs.&#xD;
  &#xD;
            -  Participants taking medications that are contraindicated with any of the study drugs,&#xD;
               such as monoamine oxidase (MAO) inhibitors or tricyclic antidepressants.&#xD;
  &#xD;
            -  Participants who have not adhered to the pre-testing guidelines related to diet,&#xD;
               alcohol or exercise will not be excluded, but will be rescheduled for a different day.&#xD;
               This is to reduce experimental variability.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Sean van Diepen, MD, MSc</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Alberta</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Craig Steinback, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Alberta</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Emily Vanden Berg, MSc</last_name>
      <phone>(780)-492-5553</phone>
      <email>ervanden@ualberta.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Nicholas Cheung, MSc</last_name>
      <phone>(780)-492-5553</phone>
      <email>nkcheung@ualberta.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Alberta</name>
        <address>
          <city>Edmonton</city>
          <state>Alberta</state>
          <zip>T6G 2R3</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>Craig Steinback, PhD</last_name>
        <phone>(780)492-5553</phone>
        <email>craig.steinback@ualberta.ca</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <reference>
      <citation>Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach JH, Joyner MJ. Sex differences in sympathetic neural-hemodynamic balance: implications for human blood pressure regulation. Hypertension. 2009 Mar;53(3):571-6. doi: 10.1161/HYPERTENSIONAHA.108.126391. Epub 2009 Jan 26.</citation>
      <PMID>19171792</PMID>
    </reference>
    <reference>
      <citation>Steinback CD, Fraser GM, Usselman CW, Reyes LM, Julian CG, Stickland MK, Chari RS, Khurana R, Davidge ST, Davenport MH. Blunted sympathetic neurovascular transduction during normotensive pregnancy. J Physiol. 2019 Jul;597(14):3687-3696. doi: 10.1113/JP277714. Epub 2019 Jun 13.</citation>
      <PMID>31106429</PMID>
    </reference>
    <reference>
      <citation>Fairfax ST, Holwerda SW, Credeur DP, Zuidema MY, Medley JH, Dyke PC 2nd, Wray DW, Davis MJ, Fadel PJ. The role of alpha-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man. J Physiol. 2013 Jul 15;591(14):3637-49. doi: 10.1113/jphysiol.2013.250894. Epub 2013 May 7.</citation>
      <PMID>23652594</PMID>
    </reference>
    <reference>
      <citation>Dinenno FA, Eisenach JH, Dietz NM, Joyner MJ. Post-junctional alpha-adrenoceptors and basal limb vascular tone in healthy men. J Physiol. 2002 May 1;540(Pt 3):1103-10. doi: 10.1113/jphysiol.2001.015297.</citation>
      <PMID>11986395</PMID>
    </reference>
    <reference>
      <citation>Hissen SL, Taylor CE. Sex differences in vascular transduction of sympathetic nerve activity. Clin Auton Res. 2020 Oct;30(5):381-392. doi: 10.1007/s10286-020-00722-0. Epub 2020 Aug 31.</citation>
      <PMID>32865664</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 2, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>sympathetic nerve activity</keyword>
    <keyword>sex differences</keyword>
    <keyword>adrenergic receptors</keyword>
    <keyword>neurovascular transduction</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Propranolol</mesh_term>
      <mesh_term>Phentolamine</mesh_term>
      <mesh_term>Phenylephrine</mesh_term>
      <mesh_term>Isoproterenol</mesh_term>
      <mesh_term>Oxymetazoline</mesh_term>
      <mesh_term>Norepinephrine</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05997732
  org study id: Pro00126600
  nct id: NCT05997732
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Non-Randomized
  intervention model: Crossover Assignment
  intervention model description: Participants will complete three pharmacological conditions, and serve as their own controls.
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Forearm blood flow
  time frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes
  description: Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
  measure: Forearm vascular resistance
  time frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes
  description: Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
  measure: Forearm vascular conductance
  time frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes
  description: Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
  measure: Arterial blood pressure
  time frame: 10 minutes per condition + 2 minutes per agonist dose = 60 minutes
  description: Measured during resting baseline; changes during phenylephrine, isoproterenol, and norepinephrine infusion to determine agonist sensitivity.
  measure: Muscle sympathetic nerve activity
  time frame: 10 minutes per condition = 30 minutes
  description: Resting baseline
  measure: Circulating sex hormone concentrations
  time frame: 2 minutes
  description: Blood samples
  measure: Circulating sympathetic neurotransmitter concentrations
  time frame: 2 minutes
  description: Blood sample
  measure: Arterial-venous blood gas concentrations
  time frame: 2 minutes per sample = 6 minutes
  description: Blood sample during each condition
  arm group label: Control Condition
  arm group type: Experimental
  description: 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.
  arm group label: β-Adrenergic Blockade
  arm group type: Experimental
  description: 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.
  arm group label: α+β-Adrenergic Blockade
  arm group type: Experimental
  description: α-adrenoreceptors will be blocked locally in the forearm using phentolamine. Propranolol will be co-infused to maintain β-blockade.
  intervention type: Drug
  intervention name: Phenylephrine Hydrochloride
  description: Participants will receive three incremental doses via the brachial artery catheter to assess α1-adrenoreceptor mediated vasoconstriction.
  arm group label: Control Condition
  intervention type: Drug
  intervention name: Isoproterenol Hydrochloride
  description: Participants will receive four incremental doses via the brachial artery catheter to assess β-adrenoreceptor mediated vasodilation.
  arm group label: Control Condition
  intervention type: Drug
  intervention name: Norepinephrine Bitartrate
  description: Participants will receive three incremental doses via the brachial artery catheter to assess nonspecific adrenoreceptor activation.
  arm group label: Control Condition
  arm group label: β-Adrenergic Blockade
  intervention type: Drug
  intervention name: Propranolol Hydrochloride
  description: Propranolol will be continuously infused through the brachial artery catheter to induce β-adrenergic blockade locally in the forearm.
  arm group label: β-Adrenergic Blockade
  intervention type: Drug
  intervention name: Phentolamine Mesylate
  description: Phentolamine will be continuously infused through the brachial artery catheter to induce α-adrenergic blockade locally in the forearm.
  arm group label: α+β-Adrenergic Blockade
  intervention type: Drug
  intervention name: Phenylephrine Hydrochloride
  description: Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the α-adrenergic blockade.
  arm group label: α+β-Adrenergic Blockade
  intervention type: Drug
  intervention name: Isoproterenol Hydrochloride
  description: Participants will receive one dose via the brachial artery catheter to evaluate the effectiveness of the β-adrenergic blockade.
  arm group label: α+β-Adrenergic Blockade
  intervention type: Drug
  intervention name: Propranolol Hydrochloride
  description: Propranolol will be continuously co-infused with phentolamine to maintain the β-adrenergic blockade.
  arm group label: α+β-Adrenergic Blockade
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Sean van Diepen, MD, MSc
  role: Principal Investigator
  affiliation: University of Alberta
  last name: Craig Steinback, PhD
  role: Principal Investigator
  affiliation: University of Alberta
  last name: Emily Vanden Berg, MSc
  phone: (780)-492-5553
  email: ervanden@ualberta.ca
  last name: Nicholas Cheung, MSc
  phone: (780)-492-5553
  email: nkcheung@ualberta.ca
  facility: 
  contact: 
  country: Canada
  citation: Hart EC, Charkoudian N, Wallin BG, Curry TB, Eisenach JH, Joyner MJ. Sex differences in sympathetic neural-hemodynamic balance: implications for human blood pressure regulation. Hypertension. 2009 Mar;53(3):571-6. doi: 10.1161/HYPERTENSIONAHA.108.126391. Epub 2009 Jan 26.
  PMID: 19171792
  citation: Steinback CD, Fraser GM, Usselman CW, Reyes LM, Julian CG, Stickland MK, Chari RS, Khurana R, Davidge ST, Davenport MH. Blunted sympathetic neurovascular transduction during normotensive pregnancy. J Physiol. 2019 Jul;597(14):3687-3696. doi: 10.1113/JP277714. Epub 2019 Jun 13.
  PMID: 31106429
  citation: Fairfax ST, Holwerda SW, Credeur DP, Zuidema MY, Medley JH, Dyke PC 2nd, Wray DW, Davis MJ, Fadel PJ. The role of alpha-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man. J Physiol. 2013 Jul 15;591(14):3637-49. doi: 10.1113/jphysiol.2013.250894. Epub 2013 May 7.
  PMID: 23652594
  citation: Dinenno FA, Eisenach JH, Dietz NM, Joyner MJ. Post-junctional alpha-adrenoceptors and basal limb vascular tone in healthy men. J Physiol. 2002 May 1;540(Pt 3):1103-10. doi: 10.1113/jphysiol.2001.015297.
  PMID: 11986395
  citation: Hissen SL, Taylor CE. Sex differences in vascular transduction of sympathetic nerve activity. Clin Auton Res. 2020 Oct;30(5):381-392. doi: 10.1007/s10286-020-00722-0. Epub 2020 Aug 31.
  PMID: 32865664
  responsible party type: Sponsor
  mesh term: Propranolol
  mesh term: Phentolamine
  mesh term: Phenylephrine
  mesh term: Isoproterenol
  mesh term: Oxymetazoline
  mesh term: Norepinephrine