Role of Endothelin-1 in Flow-mediated Dilatation

NCT02086253 | Completed

• 2 other identifiers: 2013/161/HP2013-004425-87
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Endothelial dysfunction of conduit arteries contributes to the increased morbidity and cardiovascular mortality in patients with essential hypertension and appears increasingly as an independent therapeutic target. We have shown previously that besides a decrease in the availability of NO and other endothelium-derived vasodilators factors, the epoxyeicosatrienoic acids, an increase in the vasoconstrictor endothelin-1 (ET-1) may play a role in the pathophysiology of this endothelial dysfunction. Indeed, the local concentrations of endothelin-1 during the endothelium-dependent dilation of the radial artery in response to a sustained increase in blood flow decreased significantly in healthy volunteers controls but not in hypertensive patients. This lack of adaptation of the endothelinergic system could be due to a decreased clearance of endothelin-1 by endothelial ETB receptors, potentiating the vasoconstrictor action of endothelin-1 mediated by ETA receptor activation at the muscular level. However, to validate this hypothesis , it is needed to demonstrate the physiological role of ETA receptor and ETB in sustained flow-mediated dilatation of conduit arteries.

Conditions

Healthy Conditions

Keywords

Endothelin, endothelium, flow-mediated dilatation

Outcome Measures

Primary Outcomes (1)

• Effect of ETB receptor blockade on flow-mediated dilatation

  This study will evaluate the effect of the ETB receptor blockade on the magnitude of the flow-mediated dilatation of the radial artery in response to distal skin heating in 8 healthy subjects. Radial artery diameter and blood flow will be measured by high-resolution echotracking coupled to Doppler.

  One hour after BQ-788 brachial infusion

Secondary Outcomes (2)

• Effect of ETA and ETA/ETB receptor blockade on flow-mediated dilatation

  One hour after BQ-123 alone or with BQ-788 brachial infusion

• Effect of ETA and/or ETB receptor blockade on ET-1, NO and EET bioavailability

  One hour after BQ-788 and/or BQ-123 brachial infusion

Study Arms (3)

BQ-788

EXPERIMENTAL

Effect of BQ-788 on the magnitude of sustained flow-mediated dilatation

Drug: BQ-788 and/or BQ-123

BQ-123

EXPERIMENTAL

Effect of BQ-123 on the magnitude of sustained flow-mediated dilatation

Drug: BQ-788 and/or BQ-123

BQ-788 + BQ-123

EXPERIMENTAL

Effect of BQ-788+BQ-123 on the magnitude of sustained flow-mediated dilatation

Drug: BQ-788 and/or BQ-123

Interventions

BQ-788 and/or BQ-123 DRUG

BQ-123; BQ-788; BQ-788 + BQ-123

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male, Caucasian, aged 18 to 35 years
• Non-Smoking
• Resting heart rate\> 50 and \<90 bpm
• SBP \<140 mmHg and DBP \<90 mm Hg at rest in the supine position for 10 minutes
• Normal ECG

You may not qualify if:

• Known allergy
• Intolerance to glyceryl trinitrate
• Intolerance to lidocaine
• Family history of hypertension
• Excessive alcohol consumption ( more than 50 g / day)
• Addiction or presumption of illicit drug use
• Subject refusing blood samples for serology of hepatitis B , C and HIV
• History of illness or psychological or sensory abnormality that may prevent the subject to understand the requirements for participation in the protocol or prevents giving informed consent
• Metabolic or endocrine disease
• Immunological diseases
• Renal or hepatic impairment
• Ischemic or obstructive heart disease
• Neoplastic disease
• Gastrointestinal disease
• Neurological disease , intracranial hypertension , seizure disorders

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

CHU - Hôpitaux de Rouen

Rouen, Normandy, 76031, France

Location

Related Publications (1)

• Bellien J, Iacob M, Monteil C, Remy-Jouet I, Roche C, Duflot T, Vendeville C, Gutierrez L, Thuillez C, Richard V, Joannides R. Physiological role of endothelin-1 in flow-mediated vasodilatation in humans and impact of cardiovascular risk factors. J Hypertens. 2017 Jun;35(6):1204-1212. doi: 10.1097/HJH.0000000000001307.

  PMID: 28441692 RESULT

Study Officials

• Robinson JOANNIDES, Doctor

  Chu - Hôpitaux de Rouen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2014
• First Posted: March 13, 2014
• Study Start: February 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 12, 2026

Record last verified: 2015-03

Locations

FR (1)