Protective effect of benidipine against sodium azide-induced cell death in cultured neonatal rat cardiac myocytes.
We investigated the effect of benidipine, a calcium antagonist, against sodium azide (NaN(3))-induced cell death in cultured neonatal rat cardiac myocytes with increase of LDH release, depletion of cellular ATP contents, and collapse of mitochondrial membrane potential (DeltaPsi) as indicators. Cells were treated with 1 mmol/L NaN(3) for 18 h. Benidipine concentration-dependently inhibited NaN(3)-induced cell death. The protective effect of benidipine was compared with those of amlodipine, nifedipine, candesartan, and captopril. Calcium antagonists exhibited a protective effect and the IC(50) values of benidipine, amlodipine, and nifedipine were 0.65, 90, and 65 nmol/L, respectively. NaN(3)-induced cell death was inhibited completely with the calpain inhibitor. It was considered that the sustained elevation of [Ca(2+)](i) might be implicated in NaN(3)-induced cell death. Benidipine, moreover, concentration-dependently preserved cellular ATP contents and maintained DeltaPsi the extent of the control level. In conclusion, benidipine exhibited the protective effect at an approximately 100-fold lower concentration than those of amlodipine and nifedipine in the NaN(3)-induced cardiac cell death model. It was considered that both the inhibition of Ca(2+) influx and the preservation of cellular ATP contents might play an important role in the protective effect of benidipine.
Inomata
Koji
K
Toxicological Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Ube, Yamaguchi, Japan. koji.inomata@kyowa.co.jp
Tanaka
Hiroyuki
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D017311:Amlodipine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019810:Sodium Azide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D013777:Tetrazoles / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D015853:Cysteine Proteinase Inhibitors; D004095:Dihydropyridines; D004151:Dipeptides; D013777:Tetrazoles; C071482:calpeptin; D017311:Amlodipine; C061004:benidipine; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D009543:Nifedipine; C081643:candesartan