Differential effects of 3 beta blockers on lipid peroxidation in hyperthyroid muscle.
To determine whether beta blockade protects against the acceleration of lipid peroxidation in hyperthyroid rat soleus (slow-oxidative) muscle, in vivo chronic (3 weeks) effects of 3 beta blockers with different ancillary properties on mitochondrial oxidative enzymes, antioxidant enzymes, and thiobarbituric acid-reactive substances were investigated. The rats were rendered hyperthyroid by the administration of thyroxine and treated simultaneously with either carteolol (a nonselective blocker with partial agonist activity; 30 mg/kg/day), atenolol (a beta 1-selective blocker; 50 mg/kg/day), or arotinolol (a nonselective blocker with weak alpha-blocking action; 50 mg/kg/day) over a 3 week period. Hyperthyroidism induced tachycardia, an increase in the mitochondrial oxidative enzymes, manganese (mitochondrial) superoxide dismutase and thiobarbituric acid-reactive substances, and a decrease in the other antioxidant enzymes. The tachycardia was alleviated completely by either atenolol or arotinolol, but partially by carteolol. Arotinolol, but neither carteolol nor atenolol, inhibited the increase in oxidative enzymes and thiobarbituric acid-reactive substances. The levels of antioxidant enzymes were minimally affected by the beta-blocker treatment. Beta 2-, and possibly alpha- as well, but not beta 1-, blockade suppressed mitochondrial hypermetabolism and protected against peroxidative injury in the hyperthyroid soleus muscle. Partial agonist activity was not beneficial.
Asayama
K
K
Department of Pediatrics, Yamanashi Medical College, Japan.
Hayashibe
H
H
Dobashi
K
K
Kato
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002354:Carteolol / Q000494:pharmacology; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D013858:Thiobarbiturates; C024523:arotinolol; D001262:Atenolol; D002354:Carteolol; C029684:thiobarbituric acid