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The Role of Cyclooxygenase Activity in the Endothelial Function of Hypertensive and Hypercholesterolemic Patients

This study has been completed.
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: January 2000

A layer of cells called the endothelium line the walls of blood vessels. These cells produce substances that control the tone of blood vessels and thus control blood flow through the vessel. This regulating activity of the endothelium is dysfunctional in several diseases of the heart and blood vessels, including high blood pressure and high levels of cholesterol.

Previous research has pointed toward a decrease in the action of nitric oxide (NO) as the cause of this abnormality. Nitric oxide is a substance produced by the cells of the endothelium that plays a role in the relaxation of blood vessels.

In this project researchers plan to study blood flow through the blood vessels in patients forearms after receiving four different drugs: sodium nitroprusside, acetylcholine, L-NMMA, and aspirin. These four drugs act on the blood vessels of the forearm through different mechanisms. Acetylcholine and sodium nitroprusside are drugs that open the blood vessels of the forearm and increase blood flow through the vessel. L-NMMA is a drug that blocks production of nitric oxide (NO). Aspirin's role in controlling blood flow is unknown.

Patients participating in this research study will not directly benefit from it. However, the study will contribute to researchers understanding of diseases of the blood vessels and heart.

Healthy Hypercholesterolemia Hypertension

Study Type: Observational
Official Title: The Role of Cyclooxygenase Activity in the Endothelial Function of Hypertensive and Hypercholesterolemic Patients

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 75
Study Start Date: February 1998
Estimated Study Completion Date: January 2001
Detailed Description:

The endothelium modulates vascular tone by the release of constricting and relaxing substances that act on the underlying smooth muscle. This regulatory activity of the endothelium is dysfunctional in a number of cardiovascular conditions, including essential hypertension and hypercholesterolemia. Previous studies from our group have implicated a decreased action of endothelium-derived nitric oxide (NO) as the mechanism responsible for this abnormality. Whether this reduced bioactivity of NO is related to vasoactive prostanoids remains uncertain.

We propose to test the hypothesis that an increased production of vasoactive prostanoids by the cyclooxygenase (COX) system is responsible for the reduced bioactivity of NO in essential hypertension and hypercholesterolemia. We will investigate the effect of COX inhibition by aspirin (ASA) on resting vascular tone, and on both endothelium-dependent and independent vasodilation in normal subjects, hypertensive patients, and hypercholesterolemic patients.

For this purpose, we propose to analyze the regional vascular responses to acetylcholine (ACH) and to sodium nitroprusside (SNP) before and after the administration of ASA. We will also analyze the basal forearm blood flow (FBF) responses to increasing doses of ASA infusion. We will employ infusion of drugs into the brachial artery and we will measure the responses of the forearm vasculature by means of strain gauge plethysmography.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Patients (men and nonpregnant women) with systemic hypertension and patients with hypercholesterolema will be included for this study.

Patient with aspirin allergies and those with a platelet count less than 50,000 will be excluded.

Volunteers cannot be in any kind of medication while participating in this study.

No history of diabetes, peripheral vascular disease, coagulopathy, or vasculitis.

Must be capable of rendering informed consent for all procedures.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00001742

United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Publications: Identifier: NCT00001742     History of Changes
Other Study ID Numbers: 980064
Study First Received: November 3, 1999
Last Updated: March 3, 2008

Keywords provided by National Institutes of Health Clinical Center (CC):
Nitric Oxide
Sodium Nitroprusside

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Lipid Metabolism Disorders
Metabolic Diseases processed this record on September 18, 2017