Role of Endothelin in the Regulation of Vascular Tone in Patients With Essential Hypertension

Completed

• Conditions: Hypertension

• Registration Number: NCT00001527
• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary

Endothelin-1 (ET-1) is a powerful vasoconstricting peptide produced predominantly by vascular endothelial cells, that exerts its effect through the interaction with specific receptors, ETA and ETB, on the underlying smooth muscle cells. Previous studies in normal subjects have demonstrated an increase in forearm blood flow after ET-1 antagonism, suggesting a physiologic role of ET-1 in the regulation of basal vascular tone. However, whether ET-1-mediated tone is increased in hypertensive patients is unknown.

The main purpose of this study will be to compare the forearm vascular responses to local infusion of ET-1 receptor antagonists between normotensive and hypertensive subjects in order to assess whether ET-1-mediated basal tone is increased in patients with hypertension. In addition, we propose to study the vascular responses to local ET-1 infusion to determine whether vascular smooth muscle sensitivity to this peptide is increased in hypertensive vessels. We will use both an ETA receptor antagonist, BQ-123, and an ETB receptor antagonist, BQ-788, in order to evaluate the relative contribution of the two receptor subtypes to the regulation of vascular tone.

All drugs will be infused into the brachial artery and the responses of the forearm vasculature will be measured by means of strain gauge plethysmography. Because of the relative long-lasting effect of most of the substances to be infused, the study will be performed on two separate occasions.

Detailed Description

Endothelin-1 (ET-1) is a powerful vasoconstricting peptide produced predominantly by vascular endothelial cells, that exerts its effect through the interaction with specific receptors, ETA and ETB, on the underlying smooth muscle cells. Previous studies in normal subjects have demonstrated an increase in forearm blood flow after ET-1 antagonism, suggesting a physiologic role of ET-1 in the regulation of basal vascular tone. However, whether ET-1-mediated tone is increased in hypertensive patients is unknown.

The main purpose of this study will be to compare the forearm vascular responses to local infusion of ET-1 receptor antagonists between normotensive and hypertensive subjects in order to assess whether ET-1-mediated basal tone is increased in patients with hypertension. In addition, we propose to study the vascular responses to local ET-1 infusion to determine whether vascular smooth muscle sensitivity to this peptide is increased in hypertensive vessels. We will use both an ETA receptor antagonist, BQ-123, and an ETB receptor antagonist, BQ-788, in order to evaluate the relative contribution of the two receptor subtypes to the regulation of vascular tone.

All drugs will be infused into the brachial artery and the responses of the forearm vasculature will be measured by means of strain gauge plethysmography. Because of the relative long-lasting effect of most of the substances to be infused, the study will be performed on two separate occasions.

Study Timeline

• Study Start: 1995-11
• Status Verified: 1999-11
• Study First Submitted: 1999-11-03
• Study Completion: 2000-09
• Study First Submitted QC: 2002-12-09
• Study First Posted: 2002-12-10
• Last Update Submitted: 2008-03-03
• Last Update Posted: 2008-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

National Heart, Lung and Blood Institute (NHLBI); 🇺🇸 Bethesda, Maryland, United States