Endothelin Receptor Function and Acute Stress

N/AActive Not RecruitingNCT02116335

Augusta University320 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

320

Conditions

Hypertension

Interventions

BosentanDRUG

Stress response and vascular function will be assessed 3 days following 125 mg twice per day of Bosentan

PlaceboDRUG

Stress response and vascular function will be assessed 3 days following twice per day placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

Georgia Regents University

Augusta, Georgia, United States

Outcomes

Primary Outcomes

Flow-Mediated Dilation (FMD)

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