To determine whether beta-blockade protects rat heart against
thyroxine (T4)-induced accelelation of lipid peroxidation, in vivo effects of 3 beta-blockers with different ancillary properties on the mitochondrial oxidative
enzyme,
antioxidant enzymes and
lipid peroxide were investigated. The rats were rendered
hyperthyroid by adding T4 to their
drinking water for 3 weeks and were treated simultaneously with either
carteolol (a blocker with partial agonist activity; 30 mg/kg/day),
atenolol (50 mg/kg/day) or
arotinolol (a blocker with weak alpha-blocking action; 50 mg/kg/day). The T4-induced
tachycardia was alleviated completely by either
atenolol or
arotinolol, but only partially by
carteolol.
Cytochrome c oxidase activity in the heart muscle was increased by T4 with a parallel increase in
manganese (mitochondrial)
superoxide dismutase.
Atenolol, but neither
carteolol nor
arotinolol, suppressed this increase. Similarly, the T4-induced acceleration of lipid peroxidation was suppressed by
atenolol alone.
Glutathione peroxidase was markedly decreased, and both
copper zinc (cytosolic)
superoxide dismutase and
catalase were also decreased or tended to be decreased by T4. The levels of these 3
enzymes were only minimally affected by the beta-blocker treatments. These results suggest that beta-blockade suppresses mitochondrial hypermetabolism and protects heart muscle against oxidative stress in
hyperthyroidism, and that the ancillary properties of beta-blockers such as partial agonist activity and alpha-blocking action negate the protection.