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

Primary Purpose

Hypertension

Status
Completed
Phase
Locations
United States
Study Type
Observational
Intervention
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Hypertension focused on measuring BQ-123, BQ-788, Endothelin, Endothelium, Plethysmography, Essential Hypertension

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Between 40-65 years old. Normal Volunteers who are not taking medications. Have no medical problems. Cholesterol below 200 mg/dl. No contraceptives. Hypertensive Patients with blood pressure greater than 145/90 off medications. Serum cholesterol less than 200 mg/dl. No other medical problems. High cholesterol patients with cholesterol level greater than 250 mg/dl. No other medical problems.

Sites / Locations

  • National Heart, Lung and Blood Institute (NHLBI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001527
Brief Title
Role of Endothelin in the Regulation of Vascular Tone in Patients With Essential Hypertension
Official Title
Role of Endothelin in the Regulation of Vascular Tone in Patients With Essential Hypertension
Study Type
Observational

2. Study Status

Record Verification Date
November 1999
Overall Recruitment Status
Completed
Study Start Date
November 1995 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
September 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
BQ-123, BQ-788, Endothelin, Endothelium, Plethysmography, Essential Hypertension

7. Study Design

Enrollment
60 (false)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Between 40-65 years old. Normal Volunteers who are not taking medications. Have no medical problems. Cholesterol below 200 mg/dl. No contraceptives. Hypertensive Patients with blood pressure greater than 145/90 off medications. Serum cholesterol less than 200 mg/dl. No other medical problems. High cholesterol patients with cholesterol level greater than 250 mg/dl. No other medical problems.
Facility Information:
Facility Name
National Heart, Lung and Blood Institute (NHLBI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2451132
Citation
Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411-5. doi: 10.1038/332411a0.
Results Reference
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PubMed Identifier
7831383
Citation
Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev. 1994 Sep;46(3):325-415. No abstract available.
Results Reference
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PubMed Identifier
2175397
Citation
Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20-27;348(6303):732-5. doi: 10.1038/348732a0.
Results Reference
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Role of Endothelin in the Regulation of Vascular Tone in Patients With Essential Hypertension

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