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
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
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
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.
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
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.