CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 3, April 2013
60
AFRICA
disodiumhydrogen phosphate, 90ml distilledwater).The samples
were sectioned, stained and processed for histopathological
evaluation. The organs were processed, sectioned at 5-
μ
m
thickness and stained with standard haematoxylin and eosin.
The slides were mounted and evaluated under a microscope by a
qualified pathologist.
The histological evaluation was performed to compare the
changes induced in untreated and treated AABIH rats with AT
1
receptor blockers in comparison with the control, sham-operated
rat organs (heart, liver, kidneys and thoracic aorta).
Statistical analysis
The values are expressed as mean
±
SEM. Data were analysed by
analysis of variance (ANOVA) followed by Tukey’s multiple-
comparison test to compare the treatment groups with the control
group using a GraphPad Prism.
Results
The sham-operated control (normotensive) group, AABIH rats,
and the groups treated with AT
1
receptor antagonists (losartan,
candesartan and irbesartan) were monitored periodically. In
terms of general appearance and behaviour, nothing unusual was
noted in any of the treatment groups. The body weight gain in
both the treated and untreated groups was slightly lower than
in their respective control groups, but the differences were not
significant (
p
>
0.05). Mortality in the AAB animals during or
immediately after surgery was about 20%. Another 15% of the
animals died within 24 hours of surgery.
In the AABIH group, there was a significant increase in
systolic blood pressure from weeks 3 to 16 (
p
<
0.001) compared
to the control, sham-operated group. Significant reduction
in the systolic blood pressure was observed in the losartan-,
candesartan- (
p
<
0.001) and irbesartan-treated (
p
<
0.05) groups,
compared with the AABIH group (Table 1).
In the AABIH group, there was a significant (
p
<
0.001)
decrease in catalase activity compared to the control, sham-
operated group. In the groups treated with losartan (
p
<
0.001)
and irbesartan (
p
<
0.05), there was a significant increase in
the level of catalase activity compared with the AABIH group.
However, there was no significant increase in catalase activity in
the candesartan group (
p
>
0.05) (Table 2).
In the AABIH group, there was a significant reduction in
SOD activity when compared to the control, sham-operated
group. A significant increase (
p
<
0.001) in serum SOD activity
was observed in the losartan-, candesartan- and irbesartan-
treated groups, compared to the AABIH group (Table 2).
Histopathological evaluation
Histological sections from the normal control, sham-operated
rat hearts showed normal structure and architecture. Heart
sections of the untreated AABIH rats showed mild to moderate
degrees of haemorrhage (accumulation of red blood corpuscles
in between the cardiac fibres), mild perivascular fibrosis (fibrous
tissue proliferation around the blood vessels), defragmentation
of cardiac fibres (loss of striations), congestion (accumulation of
red blood cells in the blood vessels in the parenchyma), oedema
(separation of cardiac fibres), and mild vacuolations and focal
areas of necrosis in one or two areas. The tissue also showed
mild lymphocytic infiltration (Fig. 1A, B).
Compared to the untreated AABIH group, the losartan-treated
group showed a mild degree of haemorrhage, mild perivascular
fibrosis, defragmentation of the cardiac fibres, congestion,
oedema and mild vacuolations. The tissue also showed mild
lymphocytic infiltration. The candesartan-treated group showed
a mild-to-moderate degree of haemorrhage, mild perivascular
fibrosis, and defragmentation of cardiac fibres, congestion,
oedema, moderate vacuolations and focal areas of necrosis in
one or two areas. The irbesartan-treated group showed mild-to-
moderate degrees of haemorrhage, mild-to-moderate oedema,
and separation of cardiac fibres and congestion (Fig. 1C–E)
The sections of normal control, sham-operated rat livers
showed normal structure and architecture. Liver sections of the
untreated AABIH rats showed congestion, multifocal areas of
necrosis, and dilation of the central vein. There was also a severe
degree of degeneration and vacuolations restricted to the border
TABLE 1. EFFECT OFAT
1
RECEPTORANTAGONISTS
ON SYSTOLIC BP OFAABIHAND CARDIAC
HYPERTROPHY RATS
Treatment
Systolic BP
(mmHg)
week 1
Systolic BP
(mmHg)
week 16
% Increase in
systolic BP
week 16
Control
94.14
±
0.589 105.9
±
0.7004 12.96
±
1.21
Hypertensive
114.5
±
0.816
149.3
±
0.821
#
158.7
±
2.194 39.37
±
1.494
Losartan
114.4
±
0.9197 120.3
±
4.113 6.144
±
3.66***
Candesartan
104.8
±
1.880 126.0
±
2.481 14.04
±
3.98***
Irbesartan
102.8
±
0.427 126.7
±
1.298 23.75
±
0.895*
AABIH
=
abdominal aortic banding-induced hypertension.
Values are expressed in mean
±
SEM,
n
=
8. Statistical analysis: one-way
analysis of variance (ANOVA) followed by Tukey’s multiple comparison
test.
*Statistically significant decrease in systolic BP compared with hyperten-
sive group (
p
<
0.05).
**Statistically significant decrease in systolic BP compared with hyper-
tensive group (
p
<
0.01).
***Statistically significant decrease in systolic BP compared with hyper-
tensive group (
p
<
0.001).
#
Systolic blood pressure during week 3. The patency of the hypertension
induced by abdominal aortic banding was ascertained during week 3.
TABLE 2. EFFECT OFAT
1
RECEPTORANTAGONISTS ON
SERUM SODAND CATALASE LEVELS IN THE PRESSURE-
OVERLOADAABIHAND CARDIAC HYPERTROPHY RATS
Treatment
SOD (units /ml)
Catalase (units /ml)
Control
19.61
±
0.4095
160.0
±
5.768
Hypertensive
12.92
±
0.4601
144.7
±
2.204
Losartan
35.55
±
1.622***
202.0
±
3.539***
Candesartan
25.72
±
1.586***
146.6
±
1.997
Irbesartan
27.74
±
0.7738***
176.2
±
4.043*
AABIH
=
abdominal aortic banding-induced hypertension.
Values are expressed in mean
±
SEM,
n
=
8. Statistical analysis: one-way
analysis of variance (ANOVA) followed by Tukey’s multiple comparison
test.
*Statistically significant decrease in systolic BP compared with hyperten-
sive group (
p
<
0.05)
**Statistically significant decrease in systolic BP compared with hyper-
tensive group (
p
<
0.01)
***Statistically significant decrease in systolic BP compared with hyper-
tensive group (
p
<
0.001).
