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Impaired function of the
endothelium, which is
the innermost cell layer
of the arteries, is an
initial step in the
development of
atherosclerosis. The
degree of endothelial
dysfunction is
believed to predict
future cardiovascular
events such as heart
attack and stroke.
Pycnogenol®
is an extract from the
bark of the French
maritime pine (Pinus
pinaster). It is rich in
watersoluble
polyphenol compounds
including procyanidins,
catechin, taxifolin and
phenolcarbonic acids
that have antioxidant
and anti-inflammatory
activity. Pycnogenol may
influence endothelial
function by stimulating
endothelial nitric oxide
synthase with the result
of elevated nitric oxide
levels. The purpose of
this clinical trial was
to investigate the
effects
of Pycnogenol on
endothelial function in
healthy men.
This randomized,
double-blind,
placebo-controlled trial
was conducted at the
Hiroshima
University Graduate
School of Biomedical
Sciences in Hiroshima,
Japan. The subjects were
16 healthy young men.
The subjects were
randomly assigned to
take either 180 mg
Pycnogenol (Horphag
Research, Ltd., Geneva,
Switzerland) or a
placebo every morning
for 2
weeks. Changes in basal
forearm blood flow
(vasodilation) were
measured after subjects
were given infusions of
acetylcholine, which is
an endothelium-dependent
vasodilator, and
sodium nitroprusside,
which is an
endothelium-independent
vasodilator. Forearm
blood flow
was measured by
strain-gauge
plethysmography at
baseline and after 2
weeks of treatment
with Pycnogenol or
placebo. To evaluate the
effect of Pycnogenol on
the release of nitric
oxide, subjects were
given an infusion of
N-monomethyl-L-arginine
(L-NMMA) along with
acetylcholine. L-NMMA
blocks the nitric oxide
synthase enzyme that
produces nitric oxide.
Plasma levels of
8-hydroxy-2'-deoxyguanosine
(8-OHdG) were measured
as a marker of
oxidative stress.
Basal forearm blood flow
was unaffected after two
weeks in both groups.
Infusion of
acetylcholine increased
forearm blood flow
before and after
treatment in both
groups.
Pycnogenol significantly
enhanced the
vasodilation response to
acetylcholine (P <
0.05),
whereas the placebo had
no effect. Infusion of
sodium nitroprusside
also increased forearm
blood flow before and
after treatment in both
groups, but neither
Pycnogenol nor placebo
had
any additional effect.
The infusion of L-NMMA
with acetylcholine
blocked the vasodilating
effect of acetylcholine
and decreased forearm
blood flow. L-NMMA also
eliminated the
enhancement of
acetylcholine-induced
vasodilation by
Pycnogenol. No
significant changes in
arterial blood pressure
or heart rate occurred
in the subjects during
any of the infusions.
Plasma levels of 8-OhdG
were unchanged in both
groups.
These results
demonstrate that Pycnogenol enhances
endothelium-dependent
vasodilation but
not
endothelium-independent
vasodilation. The
blunting of
Pycnogenol-stimulated
vasodilation by a
substance that inhibits
nitric synthase suggests
that the mechanism of
action
for Pycnogenol is
augmented nitric oxide
production. In vitro
studies have shown that
plant
polyphenols enhance
expression of nitric
oxide synthase genes,
resulting in release of
nitric
oxide from endothelial
cells. Thus, Pycnogenol
may have a direct
ability to increase
nitric
oxide production.
The authors conclude
that Pycnogenol augments
endothelium-dependent
vasodilation
through an increase in
nitric oxide production.
Healthy endothelial
function is dependent
upon a balance between
reactive oxygen species
and nitric oxide, and
therefore Pycnogenol
may be useful in the
treatment of
cardiovascular disease
and other diseases
involving
oxidative stress.
The authors recommend
that future studies
should measure urinary
excretion of 8-OhdG, a
more sensitive marker of
oxidative stress than
plasma levels, to
provide more information
about the antioxidant
effects of Pycnogenol.
Future studies should
also involve a larger
number of subjects and
study populations other
than healthy young men,
particularly those
with greater oxidative
stress demonstrated by
higher basal 8-OhdG
levels.
—Heather S. Oliff, PhD
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