CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 1, February 2012
18
AFRICA
Amlodipine attenuates oxidative stress in the heart and
blood of high-cholesterol diet rabbits
I SALEHI, M MOHAMMADI, F MIRZAEI, FG SOUFI
Summary
Introduction:
Oxidative stress is a key component of athero-
sclerosis. It has been suggested that amlodipine inhibits
oxidative stress. In this study, we evaluated the effects of
amlodipine on the total antioxidant capacity of heart tissue
and blood in 36 control and cholesterol-fed male New
Zealand white rabbits.
Methods:
The rabbits were divided into four groups (
n
=
9).
Group 1 rabbits were fed a regular diet, group 2 were fed
a diet with 2% cholesterol, group 3 were fed a regular diet
plus 5 mg/kg/day oral amlodipine, and group 4 were fed 2%
cholesterol diet plus amlodipine 5 mg/kg/day. At the end
of eight weeks, blood samples were drawn and at the same
time heart tissue was isolated and frozen in liquid nitrogen.
After homogenisation, the solution was centrifuged and the
light supernatant was stored at –80˚C. This was used for
determination of glutathione peroxidase (GPX), superoxide
dismutase (SOD) and (MDA) levels.
Results:
Eight weeks of amlodipine treatment significantly
reduced the levels of total cholesterol, low-density lipoprotein
cholesterol and triglycerides in the group on the hypercholes-
terolaemic diet (
p
<
0.05). In the blood, the level of thiobar-
bituric acid-reactive substances increased in the rabbits on
the 2% cholesterol diet (group 2) and 2% cholesterol-plus-
amlodipine diet (group 4) and decreased in the amlodipine-
only group (group 3) (
p
<
0.05). Lipid peroxidation in the
heart tissue was similar to that in the blood, except in the
amlodipine-only group (group 3). In the blood, the activ-
ity of total SOD (tSOD) decreased in the group on the 2%
cholesterol diet (group 2) (
p
<
0.05) and markedly increased
in the amlodipine-only (group 3) and 2% cholesterol-plus-
amlodipine groups (group 4) (
p
<
0.05).
Conclusion:
Amlodipine decreased oxidative stress in the
heart and blood and improved the lipid profile in cholesterol-
fed rabbits. Therefore, it may be considered a useful tool for
the reduction of oxidative stress and improvement of lipid
profiles in diseases related to atherosclerosis.
Keywords:
oxidation stress, cholesterol-fed rabbits, lipid peroxi-
dation, amlodipine
Submitted 21/2/10, accepted 26/11/10
Cardiovasc J Afr
2012;
23
: 18–22
DOI: 10.5830/CVJA-2010-091
Oxidative stress, an imbalance between the production of reac-
tive oxygen species (ROS) and their detoxification by antioxi-
dants, is involved in cardiovascular diseases such as atheroscle-
rosis, hypertension and heart disease.
1,2
ROS cause oxidation
of membrane phospholipids, proteins and DNA,
3
and result in
contractile failure and apoptosis in cardiomyocytes.
1,4
But short-
term oxidative stress may also be important in the prevention of
aging by the induction of a process called mitohormesis. ROS
can also be beneficial as they are used by the immune system to
attack and kill pathogens.
2
Atherosclerosis represents a state of heightened oxidative
stress characterised by lipid oxidation in the vascular wall.
5
Overproduction of ROS under pathophysiological conditions is
an important part of atherosclerosis. Therefore oxidative stress
is considered to play a key role in the pathogenesis of athero-
sclerosis.
6,7
It has been proposed that oxidative stress plays an important
role in the inflammatory processes that are key components of
atherosclerosis.
8
Under physiological conditions, the toxic effects
of ROS can be reduced by enzymatic and non-enzymatic anti-
oxidants.
9
Superoxide dismutase (SOD), glutathione peroxidase
(GPX) and catalase (CAT) provide the first line of enzymatic
antioxidant defence against ROS-mediated cardiac injury.
1,10
To improve the prognosis of patients with heart disease and
injury, novel therapeutic strategies have focused on regulating
oxidative stress in the cardiovascular system. Since both oxida-
tive stress and inflammation need the participation of calcium
ions (Ca
2+
) to cause atherosclerosis, calcium channel blockers
(CCBs) are widely used in the cardiovascular field for the control
of angina and hypertension and as an alternative to
β
-blockers in
patients with heart failure.
11,12
Amlodipine, a third-generation dihydropyridine CCB, has a
high affinity for the lipid constituents of the cellular membrane.
There is much basic and clinical data indicating that amlodipine,
in addition to having haemodynamic properties, exerts non-
calcium channel-related modulation in the vasculature, such as
antioxidant activity.
13
Since the antioxidant activity of amlodi-
pine, particularly in the heart, has not yet been well examined,
we aimed to investigate the role of amlodipine in the heart and
blood of rabbits.
Methods
Thirty-six male New Zealand white rabbits (
±
1.4 kg) were
obtained from the laboratory animal house of Tabriz University
of Medical Sciences. They were housed in an animal room at
22–24ºC and given free access to commercial rat chow and tap
water. All the experimental procedures used, as well as rabbit care
Department of Physiology, Faculty of Medicine, Hamadan
University of Medical Sciences, Hamadan, Iran
I SALEHI, PhD
Drug Applied Research Center, Tabriz University of Medical
Sciences, Tabriz, Iran
M MOHAMMADI, PhD,
F MIRZAEI, MSc
Lung and Tuberculosis Research Center, Tabriz University
of Medical Sciences, Tabriz, Iran
FG SOUFI, PhD
