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Endothelin Receptor Function and Acute Stress

Not Applicable
Active, not recruiting
Conditions
Hypertension
Interventions
Drug: Placebo
Registration Number
NCT02116335
Lead Sponsor
Augusta University
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
320
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboStress response and endothelial function will be determined following a three day treatment of placebo
BosentanBosentanSub-Chronic (3 days) Bosentan 250mg/day.
Primary Outcome Measures
NameTimeMethod
Flow-Mediated Dilation (FMD)Baseline and 3 days

Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function.

Secondary Outcome Measures
NameTimeMethod
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 FlowBaseline 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.

Femoral blood flowBaseline 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.

Blood PressureBaseline 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.

Resting Energy ExpenditureBaseline and 3 days

REE will be assessed before and following treatment

Trial Locations

Locations (1)

Georgia Regents University

🇺🇸

Augusta, Georgia, United States

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