Hot Flashes and Neurovascular Function in Women

Study Overview
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Brief Summary
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Women who experience hot flashes are at greater risk for hypertension and other cardiovascular disease. Neurovascular control mechanisms are likely to play an important role in this relationship. As such, these studies are designed to provide a major step forward in understanding the link between hot flashes and neurovascular dysfunction and, by extension, cardiovascular disease in women.

Official Title
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Hot Flashes and Neurovascular Function in Women

Conditions
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Hot Flashes, Menopause, Vasomotor System; Labile

Intervention / Treatment
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* Other: Sympathoexcitatory stressors
* Drug: Sodium Nitroprusside
* Drug: Acetylcholine
* Drug: Terbutaline
* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smokers. Non-obese. Have at least one ovary. Free from cardiovascular disease. Not taking medications influencing cardiovascular function. Exclusion Criteria: - None.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Experimental: Healthy Women Volunteers<br>Hot Flash frequency will be assessed in the study subjects during a screening period. Participants can then chose to participate 1 or 2 study visits- Protocol 1: Microvascular function and/or Protocol 2: Autonomic function | Other: Sympathoexcitatory stressors<br>* Muscle sympathetic nerve activity will be measured continuously at baseline and in response to sympathoexcitatory stressors, including a Valsalva maneuver, isometric handgrip exercise, a cold pressor test, and stepped hypercapnia.<br>* Other names: Valsalva maneuver, handgrip exercise, ice water, and hypercapnia;Drug: Sodium Nitroprusside<br>* Sodium nitroprusside, used to test endothelium-independent vasodilation, will be infused through a brachial artery catheter at 0.25, 0.5, 1.0 and 2.0 ug/100ml tissue/min.<br>* Other names: Forearm vascular conductance response to sodium nitroprusside;Drug: Acetylcholine<br>* Acetylcholine, used to test endothelium-dependent vasodilation, will be infused through a brachial artery catheter at 1.0, 2.0, 4.0, and 8.0 μg/100ml tissue/min<br>* Other names: Forearm vascular conductance response to acetylcholine;Drug: Terbutaline<br>* Terbutaline, a β2-Adrenergic selective agonist, will be infused through a brachial artery catheter at 0.1, 0.5, 1.0, and 2.0 μg/100ml tissue/min.<br>* Other names: Forearm vascular conductance response to terbutaline;Drug: Norepinephrine<br>* Norepinephrine, an α-adrenergic vasoconstricting agent, will be infused through a brachial artery catheter at 1.0, 2.0, 4.0, and 8.0 ng/100ml tissue/min<br>* Other names: Forearm vascular conductance response to norepinephrine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare microvascular function in women with low and high frequency hot flashes | Change in forearm vascular conductance with intra-arterial drug infusions. Vascular conductance is an index of vascular tone and is assessed using a technique called venous occlusion plethysmography | Continuous measurement of vascular conductance during infusion of each drug- 3min at baseline and at each drug dose ( 60min total of continuous forearm vascular conductance measurements) | 
| Compare sympathetic function in women with low and high frequency hot flashes | Muscle Sympathetic Nerve Activity will be directly using a technique called microneurography. | Continuous measurement of muscle sympathetic nerve activity at rest and in response to stressors ( 75min of continuous data collection once a sympathetic nerve signal is found) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autonomic function, Microvascular Function, Neurovascular function