Azelnidipine inhibits H2O2-induced cell death in neonatal rat cardiomyocytes.
OBJECTIVE
Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Azelnidipine is a novel dihydropyridine calcium channel blocker. Several studies have demonstrated that some dihydropyridine calcium channel blockers have antioxidant effects. We evaluated the antioxidant effects of azelnidipine compared to another dihyropyridine calcium channel blocker, nifedipine, in neonatal rat cardiomyocytes.


METHODS
We examined effects of azelnidipine and nifedipine on the H(2)O(2)-induced mitogen-activated protein kinase (MAPK) activity and cell death in neonatal rat cardiomyocytes.


RESULTS
Extracellular signal-regulated protein kinases (ERK), p38 MAPK and c-Jun NH(2)-terminal kinases (JNK) were activated by H(2)O(2) stimulation. Azelnidipine and nifedipine did not affect the H(2)O(2)-induced activation of ERK and p38 MAPK. In contrast, azelnidipine, but not nifedipine, inhibited the H(2)O(2)-induced JNK activation. The numbers of viable cell were significantly decreased by H(2)O(2) treatments (65.8 +/- 4.11% of control, P < 0.0001). Azelnidipine, but not nifedipine, inhibited the H(2)O(2)-induced cell death (azelnidipine: 76.0 +/- 4.66% of control, P < 0.05; nifedipine: 70.7 +/- 4.01% of control, P = 0.32).


CONCLUSIONS
Azelnidipine inhibited the H(2)O(2)-induced JNK activation and cardiac cell death. Azelnidipine may have cardioprotective effects against oxidative stress.
Koyama
Yo
Y
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan. takeishi@med.id.yamagata-u.ac.jp
Takeishi
Yasuchika
Y
Takahashi
Hiroki
H
Shishido
Tetsuro
T
Arimoto
Takanori
T
Niizeki
Takeshi
T
Harada
Mutsuo
M
Suzuki
Satoshi
S
Kitahara
Tatsuro
T
Sasaki
Toshiki
T
Kubota
Isao
I
D000818:Animals; D000831:Animals, Newborn; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D001383:Azetidinecarboxylic Acid; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D009543:Nifedipine; C061679:azelnidipine