CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 9/10, October/November 2013
AFRICA
355
Endothelial nitric oxide synthase levels and their
response to exercise in patients with slow coronary flow
HAKAN TAŞOLAR, FERHAT EYYÜPKOCA, ERDAL AKTÜRK, YASİN KARAKUŞ, MEHMET CANSEL,
JÜLİDE YAĞMUR, FATMA ÖZYALIN, BURAK ALTUN, HASAN PEKDEMİR
Abstract
Background:
Endothelial dysfunction plays a key role in the
aetiopathogenesis of slow coronary flow (SCF) even if there
is no obstructive epicardial lesion. Reduced plasma levels of
endothelial nitric oxide synthase (eNOS) are an important
indicator of endothelial dysfunction. We aimed to determine
plasma levels of eNOS and their relationship with exercise in
patients with SCF.
Methods:
Twenty-two patients with SCF in at least one coro-
nary artery and 17 healthy individuals were included in this
study. The TIMI frame count method was used to determine
SCF. Plasma levels of eNOS before and after effort were
determined in the patient and control groups.
Results:
Basal eNOS levels in the patient group were lower
than in the control group (
p
=
0.040), and plasma eNOS levels
after exercise decreased more significantly in the patient
group compared to the control group (
p
=
0.002). Median
decreases of eNOS in response to exercise were higher in
the SCF group than in the control group (
p
<
0.001), and
the decrease observed in the control group was not statisti-
cally significant (
p
=
0.35). There were significantly negative
correlations between TIMI frame count and plasma levels
of eNOS at baseline and after exercise (
r
=
–0.51,
p
=
0.015,
r
=
–0.58,
p
=
0.005, respectively). Moreover, there was also a
positive correlation between the rate–pressure product and
plasma levels of eNOS after exercise in patients with SCF
(
r
=
0.494,
p
=
0.019).
Conclusion:
Our findings indicate an important pathophys-
iological relationship between the severity of SCF in which
endothelial dysfunction plays a role in its pathogenesis and
the level of circulating plasma levels of eNOS.
Keywords:
endothelial nitric oxide synthase, slow coronary
flow, endothelial dysfunction, exercise, rate–pressure product
Submitted 12/6/13, accepted 18/9/13
Cardiovasc J Afr
2013;
24
: 355–359
DOI: 10.5830/CVJA-2013-072
Slow coronary flow (SCF), described for the first time by
Tambe and his colleagues in 1972, is an angiographic diagnosis
characterised by a low rate of flow of contrast agent in
the epicardial coronary arteries, together with typical angina
pectoris and normal coronary arteries.
1
Even though micro- and
macrovascular disease findings have been identified, such as
myofibrillar hypertrophy, myofibrillar degeneration, hyperplastic
fibromuscular thickening, luminal narrowing, endothelial
degeneration, endothelial dysfunction and diffuse atherosclerosis,
which may lead to reduced coronary flow reserve, uncertainties
still exist in the aetiopathogenesis.
2,3
Coronary blood flow and oxygen transport to the myocardium
are increased by autoregulatory mechanisms for the increased
metabolic needs associated with effort. The amount of oxygen
extracted from the blood also increases, which leads to a decrease
in the concentration of oxygen in the blood. Mitochondrial
metabolism is altered by coronary endothelium-derived nitric
oxide (NO) in an attempt to reduce the growing energy
requirements.
4,5
Vascular endothelium exhibits a number of haemostatic
functions in normal blood vessels. NO is a key molecule for
normal autoregulatory mechanisms, such as modulating the
vasodilator response to tachycardia and exercise,
6
and it has also
been found to be essential for flow-mediated dilatation of large
human arteries
in vivo.
7
Endothelial nitric oxide synthase (eNOS)
is an enzyme involved in the synthesis of NO.
8
Decreased plasma
eNOS level is an important indicator of endothelial dysfunction.
9
To our knowledge, there has been no study evaluating plasma
eNOS levels and their response to exercise in SCF patients.
Therefore we aimed to investigate the plasma levels of eNOS
before and after exercise in patients with SCF.
Methods
Twenty-two patients (19 men, three women, mean age 48.5
±
10.9 years) with angiographically proven SCF in at least one
coronary artery but normal epicardial coronary arteries were
enrolled in this study. Seventeen age- and gender-matched
patients (12 men, five women, mean age 48.7
±
9.6 years)
who had undergone coronary angiography because of typical
and quasi-typical symptoms of angina, with normal coronary
arteries and normal coronary flow on coronary angiography
comprised the control group. All control subjects had no history
of cardiovascular disease, and normal echocardiographic and
exercise studies. Because diet affects plasma eNOS levels,
10,11
Department of Cardiology, Adiyaman University, Training
and Research Hospital, Adiyaman, Turkey
HAKAN TAŞOLAR, MD,
ERDAL AKTÜRK, MD
Department of Cardiology, Faculty of Medicine, Inonu
University, Malatya, Turkey
FERHAT EYYÜPKOCA, MD
MEHMET CANSEL, MD
JÜLİDE YAĞMUR, MD
HASAN PEKDEMİR, MD
Malatya State Hospital, Malatya, Turkey
YASİN KARAKUŞ, MD
Department of Medical Biochemistry, Faculty of Medicine,
Inonu University, Malatya, Turkey
FATMA ÖZYALIN, PhD
Department of Cardiology, Faculty of Medicine, Mart
University, Canakkale, Turkey
BURAK ALTUN, MD
