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Propranolol and bepridil attenuating levothyroxine-induced rat cardiac hypertrophy and mitochondrial Ca2+
1Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
Aim:
To study the effects of propranolol and bepridil on levothyroxine-induced rat cardiac hypertrophy and mitochondrial Ca2+ Mg(2+)-ATPase activity elevation.
Methods:
Rat heart hypertrophy was induced by i.p., levothyroxine 1 mg.kg-1.d-1 x 10 d. Then rats were treated by ig propranolol (Pro) or bepridil (Bep) 10 mg.kg-1 daily. Ca2+ Mg(2+)-ATPase activity and enzyme kinetic parameters were assayed.
Results:
The activity and Vmax of mitochondrial Ca2+ Mg(2+)-ATPase isolated from hypertrophic left ventricle were 25 +/- 4 and 35.1 +/- 0.8 mumol Pi.h-1/mg protein, respectively, those of normal were 6.7 +/- 1.8 and 10 +/- 4 mumol Pi.h-1/mg protein, respectively. Apparent K(m) of the hypertrophic group Ca2+ Mg(2+)-ATPase was 0.4 +/- 0.12 mmol.L-1 ATP, and that of normal was 0.59 +/- 0.22 mmol.L-1 ATP. The total protein quantity of hypertrophic left ventricle was 80 +/- 30 mg, and that of normal was 47 +/- 9 mg. After treated with Pro or Bep (both 10 mg.kg-1 ig), the cardiac hypertrophy was attenuated, the enzyme activity and Vmax as well as total protein quantity of hypertrophic left ventricle were reduced to normal level, but apparent K(m) was not affected.
Conclusion:
Both Pro and Bep prevented the myocardium and its mitochondria from ischemia and overload calcium injury.