Role of Endothelin-1 in Flow-mediated Dilatation

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Hospital, Rouen
• Treatments: BQ 788; cyclo(Trp-Asp-Pro-Val-Leu)

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 .