Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.
We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H(2)O(2))-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H(2)O(2) (600 micromol L(-1)) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H(2)O(2) exposure. Benidipine at 1 nmol L(-1) and nifedipine at 10 nmol L(-1) decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L(-1)) significantly reduced the H(2)O(2)-induced myocardial damage. Nifedipine (10 nmol L(-1)) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H(2)O(2). The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.
Yao
Kozo
K
Drug Development Research Laboratories, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co. Ltd, 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka-ken, 411-8731, Japan. kozo.yao@kyowa.co.jp
Ina
Yasuhiro
Y
Sonoda
Rie
R
Nagashima
Ken
K
Ohmori
Kenji
K
Ohno
Tetsuji
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D009924:Organ Culture Techniques; D016877:Oxidants / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D004095:Dihydropyridines; D016877:Oxidants; C061004:benidipine; D006861:Hydrogen Peroxide