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. One of the substances produced involved in the control of blood vessel
function is nitric oxide. Nitric oxide (NO) plays a role in the relaxation of blood
Researchers have been interested in the function of the endothelium in patients with high
blood pressure (essential hypertension) and patients with high cholesterol
After conducting studies on the endothelium and nitric oxide, researchers have found that
the endothelium is indeed functioning abnormally in patients with high blood pressure and
high cholesterol. In addition, researchers have determined that the dysfunction is a result
of abnormalities in the nitric oxide (NO) system.
In this study researchers plan to investigate the relationship between blood vessel
responses in real-life settings versus laboratory settings in normal volunteers, patients
with high blood pressure, and patients with high cholesterol.
Over the last ten years, we have been interested in the investigation of endothelial
function in patients with essential hypertension and patients with hypercholesterolemia. We
have performed intra-arterial infusion of endothelium-dependent and endothelium-independent
drugs into the brachial artery with noninvasive measurement of the response of the forearm
vasculature by means of strain gauge plethysmography. Those studies have allowed us to: a)
demonstrate the presence of endothelial dysfunction in patients with essential hypertension
and in patients with hypercholesterolemia; and b) identify an abnormality in the
endothelium-derived nitric oxide system that is responsible for endothelial dysfunction in
these patients. Further studies to more precisely determine the intracellular processes
that mediate this abnormality in endothelial function in these patients are limited by the
inherent shortcomings of the in vivo technique. An alternative possibility is the study of
human small vessels in vitro; however, the relationship between in vivo and in vitro
vascular responses to endothelium-dependent and -independent agonists has not been
established. In the present study, we propose to investigate this relationship in normal
volunteers, patients with essential hypertension, and patients with hypercholesterolemia.
Patients (men and nonpregnant women) with systemic hypertension, patients with
hypercholesterolemia, and normal volunteers.
All blood pressure recordings must be consistently elevated.
No renovascular hypertension or other etiologies for elevated blood pressure.
No definite evidence of accelerated or malignant hypertension (diastolic pressures above
115 mmHg, with associated encephalopathic changes, papilledema, progressive renal failure,
or congestive heart failure), or serious intercurrent illness.
Patients in whom withdrawal of antihypertensive medications is considered hazardous are
Patients in whom the blood pressure remains at normal levels 2 weeks after withdrawal of
antihypertensive treatment will be closely monitored until they become hypertensive, at
which time they will undergo the study. Patients in whom blood pressure does not increase
after 2 months of discontinuation of therapy will be excluded from the study.
Patients with coexistent hypertension and hypercholesterolemia are ineligible.
Normal volunteers who are not taking any kind of medication are eligible.
No history of diabetes, peripheral vascular disease, coagulopathy, or any other disease
predisposing to vasculitis or Raynaud's phenomenon.
No history of keloid formation.
All patients must be capable of giving informed consent for all procedures.