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