Hypertension
Conditions
Keywords
arterial stiffness, flow-mediated dilation, endothelial function, pulse wave velocity, inflammation, oxidative stress, Nitric Oxide, Cold Pressor Test, physio flow, Bosentan, Endothelin Receptor, Endothelin-1, BMI, stress, blood pressure
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.
Interventions
DRUGBosentan
Stress response and vascular function will be assessed 3 days following 125 mg twice per day of Bosentan
DRUGPlacebo
Stress response and vascular function will be assessed 3 days following twice per day placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Augusta University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-Mediated Dilation (FMD) | Baseline and 3 days | Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arterial Stiffness Evaluation (PWV) | Baseline and 3 days | A tonometer will be gently applied on the carotid artery and then the femoral artery and the radial artery to record how fast blood flows between each of the points. |
| Physio Flow | Baseline and 3 days | Six surface electrodes will be placed on the body. 2 on the neck, 2 on the chest, and 2 on the back in order to measure parameters of the heart during exercise. |
| Blood Pressure | Baseline and 3 days | Blood pressure will measured in response to the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes. |
| Femoral blood flow | Baseline and 3 days | Though ultrasound assessment; resistance of the blood flow, blood flow, blood velocity, and arterial diameter will all be measured in the femoral artery during the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes. |
| Resting Energy Expenditure | Baseline and 3 days | REE will be assessed before and following treatment |
Countries
United States
Outcome results
None listed