Effects of beta-adrenergic blockers with different ancillary properties on lipid peroxidation in hyperthyroid rat cardiac muscle.
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.
Asayama
K
K
Department of Pediatrics, Yamanashi Medical College, Japan.
Dobashi
K
K
Hayashibe
H
H
Kato
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006980:Hyperthyroidism / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008345:Manganese / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013858:Thiobarbiturates / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D013858:Thiobarbiturates; D008345:Manganese; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; C029684:thiobarbituric acid