Long-‐life supplementation with atenolol…
259
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 mlO
2
/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 O
2
/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 O
2
/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 β-‐
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%
