Study of the Interaction Between the Cells Lining Blood Vessels and Angiotensin-Converting Enzyme

March 3, 2008 updated by: National Heart, Lung, and Blood Institute (NHLBI)

Investigation of the Interaction Between the Vascular Endothelium and Angiotensin-Converting Enzyme

The walls of blood vessels are lined by flat cells that are responsible for releasing substance(s) that control the activity of the blood vessel. These cells are referred to as the endothelium of the blood vessel. One of the substances released from the endothelium is called nitric oxide (NO). This substance functions to keep blood vessels relaxed and to prevent blood from clotting inside the vessels.

Studies done by researchers in the Cardiology Branch of the National Heart, Lung and Blood Institute have shown that nitric oxide activity may be lower in patients with hardening of the arteries (atherosclerosis) and risk factors for atherosclerosis.

Another substance released by the cells of the endothelium is called bradykinin. It functions to stimulate the production of nitric oxide. Therefore bradykinin is also responsible for the relaxation and widening of blood vessels.

An enzyme found in the blood called angiotensin-converting enzyme (ACE) inactivates baradykinin and thereby decreases the production of nitric oxide. The activity of ACE is determined by genetics and is different in each person. Medications that block ACE (ACE-inhibitors) may be useful for patients with high levels of ACE activity.

This study is designed to determine;

  1. The role of bradkinin in stimulating the production of nitric oxide
  2. Whether ACE-inhibitors improve blood vessel relaxation caused by bradykinin
  3. Whether ACE-inhibitors improve abnormal blood vessel relaxation
  4. Whether ACE-inhibitors and bradykinin affect blood clotting
  5. Whether blood vessel response to ACE-inhibitor and bradykinin depends on the patients genetic make-up

Study Overview

Status

Completed

Conditions

Detailed Description

The vascular endothelium tonically releases nitric oxide that produces smooth muscle relaxation, inhibition of platelet aggregation, and inhibition of cellular proliferation. Studies in the Cardiology Branch have demonstrated that nitric oxide activity is reduced in the coronary and peripheral vasculature of patients with atherosclerosis and in those with risk factors for atherosclerosis. Bradykinin, an endothelium-dependent vasodilator, may be an important modulator of vascular tone in vivo because it is tonically produced by the endothelium. Bradykinin is inactivated by angiotensin converting enzyme (ACE) that is found on the endothelial cell surface. The activity of plasma ACE is variable among individuals and is at least partly genetically determined. ACE activity may modulate the local vascular effects of bradykinin, and thus, ACE inhibitors would be expected to improve endothelium-dependent responses in patients with higher tissue ACE activity.

This protocol is designed to determine 1) the role of bradykinin in stimulating nitric oxide release in the human coronary and peripheral vasculature; 2) whether ACE inhibitors improve bradykinin-induced vasodilation, and if so, whether this occurs as a result of endothelium-dependent release of nitric oxide; 3) whether ACE inhibitors improve the abnormal shear-induced coronary vasodilation in patients with normal coronary arteries and those with coronary artery disease; 4) whether ACE inhibitors and bradykinin affect platelet function; 5) whether the vascular responses to ACE inhibition and bradykinin depend on the ACE genotype.

Study Type

Observational

Enrollment

209

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Heart, Lung and Blood Institute (NHLBI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Anyone with chest pain with known or suspected coronary artery disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 1995

Study Completion

April 1, 2001

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

December 9, 2002

First Posted (Estimate)

December 10, 2002

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

April 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 950099
  • 95-H-0099

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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