Adiposity and Endothelin Receptor Function

Study Overview
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Brief Summary
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Elevated levels of ET-1 have been implicated in cardiovascular disease and some forms of hypertension. Due to the strong, positive correlation between obesity and hypertension, the present study will explore the contribution of adiposity in ETB receptor function and aim to elucidate if ETB receptor dysfunction is a major contributor to hypertension in obesity.

Detailed Description
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The proposed study is designed to investigate the influence of adiposity on ETB receptor function and subsequent vascular responses. The combination of ET-1, ET-3, and the respective ETA and ETB receptor antagonists will be used to provide insight into the mechanisms of ETB receptor dysfunction in the presence of adiposity. Previous studies have revealed elevations in circulating ET-1 in obese individuals; therefore, we predict that obese subjects will exhibit 1) ETB receptor dysfuncton compared to lean subjects and 2) an improvement in ETB receptor dysfunction following treatment with Candesartan.

Official Title
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Adiposity and Endothelin Receptor Function

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Candesartan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • If you are an adult between the ages of 18-40 year old Exclusion Criteria: Evidence of cardiovascular, pulmonary, renal, hepatic, cerebral, or metabolic disease Evidence of pregnancy Using medications that affect vascular tone (i.e., nitrates, etc.) Use of any anticoagulants (i.e. aspirin) Anemia If you are postmenopausal If you have uncontrolled hypertension (treated resting SBP >140 mm Hg or DBP >90 mm Hg)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Candesartan<br>Sub chronic (7 days) Candesartan (16 mg/day) | Drug: Candesartan<br>* 7 days of Candesartan (16mg/day)<br>* Other names: Blopress, Atacand, Amias, and Ratacand;|
| Placebo Comparator: Placebo<br>Endothelial function will be determined following a seven day treatment of placebo | Drug: Placebo<br>* 7 days of Placebo<br>* Other names: Lactose capsule, Maltose capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Flow-Mediated Dilation (FMD) | Change in Brachial artery FMD induced by reactive hyperemia assessed vascular endothelial function at baseline and several hours after treatment. | pre-treatment Baseline and 7 days post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood pressure, microdialysis