Clinical trial NCT02086253: Role of Endothelin-1 in Flow-mediated Dilatation
Official title: Role of Endothelin-1 in Mediating Flow-mediated Dilatation of Conduit Arteries During Sustained Hyperemic Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Conditions
Keywords: Endothelin, endothelium, flow-mediated dilatation
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
First posted: 2014-03-13
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.


Eligibility criteria: 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 .

Primary outcomes:
measure: Effect of ETB receptor blockade on flow-mediated dilatation
timeFrame: One hour after BQ-788 brachial infusion
Secondary outcomes:
measure: Effect of ETA and ETA/ETB receptor blockade on flow-mediated dilatation
timeFrame: One hour after BQ-123 alone or with BQ-788 brachial infusion
measure: Effect of ETA and/or ETB receptor blockade on ET-1, NO and EET bioavailability
timeFrame: One hour after BQ-788 and/or BQ-123 brachial infusion
Other outcomes:
Locations:
city: Rouen
country: France
facility: CHU - Hôpitaux de Rouen
state: Normandy
Study officials:
affiliation: Chu - Hôpitaux de Rouen
name: Robinson JOANNIDES, Doctor
role: PRINCIPAL_INVESTIGATOR
References: