Role of Endothelin-1 in Flow-mediated Dilatation

University Hospital, Rouen

Status: Completed

Conditions: Healthy Conditions

Treatments: Drug: BQ-788 and/or BQ-123

Study type: Interventional

Funder types: Other

Identifiers

NCT02086253

2013-004425-87 (EudraCT Number)

2013/161/HP

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

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 .

Trial design

8 participants in 3 patient groups

BQ-788

Experimental group

Description:

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

Treatment:

Drug: BQ-788 and/or BQ-123

BQ-123

Experimental group

Description:

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

Treatment:

Drug: BQ-788 and/or BQ-123

BQ-788 + BQ-123

Experimental group

Description:

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

Treatment:

Drug: BQ-788 and/or BQ-123