Page 89 - 79_02

Long-­-life
supplementation
with
atenolol…

3.
RESULTS

The
mean
body
weight
of
the
animals
did
not
show
significant
differences

between
the
two
experimental
groups
at
the
beginning
neither
at
the
end
of
the

experiment
(results
not
shown).

No
significant
differences
were
observed
between
atenolol
and
control

animals
for
rectal
temperature
(35.24±0.1
°C
in
Old
Controls
and
35.51±0.2
in
Old

AT)
or
basal
metabolic
rate
(3.44±0.28
mlO2/g
hr
in
Old
Controls
and
3.32±0.3
in
Old

AT).

Neither
the
basal
rates
of
mtROSp
of
heart
mitochondria
(with

glutamate/malate
and
with
succinate+rotenone)
nor
the
maximal
ones
(with

glutamate/malate+rotenone)
were
significantly
modified
by
atenolol
treatment

(results
not
shown).
In
the
case
of
SKM
mitochondria
only
a
significant
decrease
with

succinate+rotenone
(from
0.92±0.07
in
Old
Controls
to
0.75±0.05
in
Old
AT
P<0.05)

was
detected.
No
significant
differences
in
mitochondrial
oxygen
consumption
were

observed
either,
except
for
significant
decreases
only
in
the
case
of
state
3
respiration

in
heart
with
both
complex
I
–linked
(glutamate/malate:
222.7±30.0
nanomoles
of
O2

/min
mg
mitochondrial
protein
in
Old
Control
and
131.8±8.7
in
Old
AT,
P<0.05)
and

complex
II-­-linked
(succinate+rotenone:
270.4±21.2
nanomoles
of
O2
/min
mg

mitochondrial
protein
in
Old
Control
and
201.4±8.8
in
Old
AT)
respiration.

Concerning
respiratory
complexes
and
AIF,
no
significant
differences
were

observed
for
any
parameter
in
the
case
of
SKM
(results
not
shown).
In
heart

mitochondria,
only
the
amount
of
complex
II
increased
from
104.0±5.8
in
Old

Controls
to
135.6±12.6
in
Old
AT
(P<0.05;
ratio
of
complex
II/porin
in
arbitrary

units),
the
rest
of
the
parameters
not
showing
significant
variations
(results
not

shown).

Atenolol
treatment
decreased
the
highly
unsaturated
22:6n-­-3
FA
and

increased
the
much
less
unsaturated
18:1n-­-9
in
heart
and
SKM
(Figure
1).
The

decrease
in
22:6n-­-3
was
of
23%
in
heart
and
of
38%
in
SKM.
Besides,
the
ratio

22:6n-­-3/24:6n-­-3,
an
index
of
the
final
steps
of
n-­-3
synthesis
through
ß-­-
peroxisomal
lipoxidation
(Figure
2)
decreased
in
both
tissues
in
the
atenolol
group

(Figure
1;
by
37%
in
SKM
and
by
46%
in
heart).

AT
animals
showed
higher
18:1n-­-9
(large
increase),
20:4n-­-6
and
24:5n-­-3,

and
lower
14:0,
20:3n-­-6
and
especially
22:6n-­-3
than
controls
(18:1n-­-9
and
22:6n-­-3

values
are
shown
in
Figure
1
while
the
other
FAs,
which
were
measured,
are
not

shown).
In
SKM,
AT
animals
showed
higher
18:1n-­-9
and
20:2n-­-6,
and
lower
22:6n-­-
3
(large
decrease)
than
controls.
The
increase
in
18:1n-­-9
was
of
30%
in
SKM
and
of

56%
in
heart.
As
a
result
of
those
changes,
the
global
indexes
of
fatty
acid

unsaturation
DBI
and
PI
were
strongly
decreased
by
the
atenolol
treatment
in
both

kinds
of
mitochondria
(Figure
3).
The
DBI
decreased
by
22%
in
SKM
and
by
11%

259