Endothelin Receptor Function and Acute Stress (End-Stress)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Augusta University
- Enrollment
- 320
- Locations
- 1
- Primary Endpoint
- Flow-Mediated Dilation (FMD)
Study Overview
Brief Summary
Our bodies respond differently to stress. Animal studies by the investigators have found that endothelin-1 plays a role in regulating blood pressure in response to stress. This study is an extension of the investigators previous animal work to evaluate the role of endothelin-1 during stress in humans.
Detailed Description
Using a salt sensitive animal model of prehypertension, the Dahl S rat,the investigators have previously published that acute stress elicits a pressor response that is accompanied by an increase in 8 isoprostane and endothelin-1. However, the pressor response is suppressed by endothelin A/B receptor antagonism. Moreover, the investigators have identified that the increase in 8-isoprostane occurs downstream of endothelin receptor activation. These data indicate that endothelin receptor activation is a main player In the pressor response to acute stress in pre-hypertensive animals; however, this phenomenon has yet to be elucidated in humans.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Men and premenopausal women (Ages 18-50 years old)
- •Self-reported Black and White adults
- •Lean adults (BMl <25 kg/m^)
- •Obese adults (BMl > 30 kg/m^)
Exclusion Criteria
- •Having a BMI less than 16 kg/m2 (severely and very severely underweight) or that is greater than 40 kg/m2 (Class III obesity)
- •Having evidence of cardiovascular, pulmonary, renal, hepatic, cerebral, or metabolic disease
- •Having evidence of pregnancy
- •Using medications that affect vascular tone (i.e., nitrates, etc.)
- •Postmenopausal women
- •Uncontrolled hypertension
- •Individuals who are on a restricted salt diet
- •Having a history of chronic pain
- •Having a history of rheumatoid arthritis
- •Using medications that are contraindicated with bosentan (i.e. glyburide, cyclosporine)
- •Liver dysfunction (which may be identified with the blood sample we take)
Arms & Interventions
Bosentan
Sub-Chronic (3 days) Bosentan 250mg/day.
Intervention: Bosentan (Drug)
Placebo
Stress response and endothelial function will be determined following a three day treatment of placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Flow-Mediated Dilation (FMD)
Time Frame: Baseline and 3 days
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function.
Secondary Outcomes
- Arterial Stiffness Evaluation (PWV)(Baseline and 3 days)
- Physio Flow(Baseline and 3 days)
- Femoral blood flow(Baseline and 3 days)
- Blood Pressure(Baseline and 3 days)
- Resting Energy Expenditure(Baseline and 3 days)
Investigators
Ryan Harris
Assistant Professor
Augusta University