Clinical trial NCT02116335: Endothelin Receptor Function and Acute Stress
Official title: Endothelin Receptor Function and Acute Stress (End-Stress)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hypertension
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
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2014-04-16
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Flow-Mediated Dilation (FMD)
timeFrame: Baseline and 3 days
Secondary outcomes:
measure: Arterial Stiffness Evaluation (PWV)
timeFrame: Baseline and 3 days
measure: Physio Flow
timeFrame: Baseline and 3 days
measure: Femoral blood flow
timeFrame: Baseline and 3 days
measure: Blood Pressure
timeFrame: Baseline and 3 days
measure: Resting Energy Expenditure
timeFrame: Baseline and 3 days
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
Study officials:
affiliation: Augusta University
name: Ryan Harris, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: