Role of Endothelin-1 in Flow-mediated Dilatation

Healthy Conditions Clinical Trial

— Endothelin  

Official title:

Role of Endothelin-1 in Mediating Flow-mediated Dilatation of Conduit Arteries During Sustained Hyperemic Stimulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02086253
• Other study ID #: 2013/161/HP
• Secondary ID: 2013-004425-87
• Status: Completed
• Phase: N/A
• First received: February 18, 2014
• Last updated: March 23, 2015
• Start date: February 2014
• Est. completion date: May 2014

Study information

• Verified date: March 2015
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• Compulsive overeating , bulimia, anorexia

• Severe psychiatric illness

• Presence of a clinically significant abnormality in laboratory tests carried out at the inclusion visit .

• HBs Ag , HCV Ab , Ac HIV 1 or HIV 2 positive .

• The use of any drug in the range of less than 5 half-life time, in particular betablockers, sildenafil, cimetidine, amiodarone .

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Conditions

Intervention

Drug:
• BQ-788 and/or BQ-123

Locations

Country	Name	City	State
France	CHU - Hôpitaux de Rouen	Rouen	Normandy

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Effect of ETA and ETA/ETB receptor blockade on flow-mediated dilatation	This study will evaluate the effect of ETA receptor and combined ETA/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-123 alone or with BQ-788 brachial infusion	No
Secondary	Effect of ETA and/or ETB receptor blockade on ET-1, NO and EET bioavailability	This study will evaluate the effect of ETA and/or ETB blockade on the variations in the local concentrations of ET-1, NO and EETs during sustained flow-mediated dilation in 8 healthy subjects. For this purpose, local blood samples will be drawn before (34°C) and at the end of hand skin heating (44°C). Plasma nitrite, indicator of NO availability will be quantified by chemiluminescence.Plasma EETs will be quantified by LC-MS. Plasma ET-1 will be quantified with an immunoassay.	One hour after BQ-788 and/or BQ-123 brachial infusion	No