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Azelnidipine Inhibits H2O2-Induced Cell Death in Neonatal Rat Cardiomyocytes

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Abstract

Purpose

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.

Materials and methods

We examined effects of azelnidipine and nifedipine on the H2O2-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 NH2-terminal kinases (JNK) were activated by H2O2 stimulation. Azelnidipine and nifedipine did not affect the H2O2-induced activation of ERK and p38 MAPK. In contrast, azelnidipine, but not nifedipine, inhibited the H2O2-induced JNK activation. The numbers of viable cell were significantly decreased by H2O2 treatments (65.8 ± 4.11% of control, P < 0.0001). Azelnidipine, but not nifedipine, inhibited the H2O2-induced cell death (azelnidipine: 76.0 ± 4.66% of control, P < 0.05; nifedipine: 70.7 ± 4.01% of control, P = 0.32).

Conclusion

Azelnidipine inhibited the H2O2-induced JNK activation and cardiac cell death. Azelnidipine may have cardioprotective effects against oxidative stress.

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Acknowledgements

We thank Sankyo Pharmaceutical Co., Tokyo, Japan for providing azelnidipine.

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Authors and Affiliations

  1. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan

    Yo Koyama, Yasuchika Takeishi, Hiroki Takahashi, Tetsuro Shishido, Takanori Arimoto, Takeshi Niizeki, Mutsuo Harada, Satoshi Suzuki, Tatsuro Kitahara, Toshiki Sasaki & Isao Kubota

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  1. Yo Koyama
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  2. Yasuchika Takeishi
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  3. Hiroki Takahashi
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  4. Tetsuro Shishido
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  5. Takanori Arimoto
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  6. Takeshi Niizeki
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  7. Mutsuo Harada
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  8. Satoshi Suzuki
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  9. Tatsuro Kitahara
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  10. Toshiki Sasaki
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  11. Isao Kubota
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Corresponding author

Correspondence to Yasuchika Takeishi.

Additional information

This study was supported in part by a grant-in-aid for Scientific Research (No. 17590702) from the Ministry of Education, Science, Sports and Culture, Japan, a grant-in-aid from the twenty-first century center of excellence (COE) program of the Japan Society for the Promotion of Science, and grants from Takeda Science Foundation and Fukuda Foundation for Medical Technology.

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Koyama, Y., Takeishi, Y., Takahashi, H. et al. Azelnidipine Inhibits H2O2-Induced Cell Death in Neonatal Rat Cardiomyocytes. Cardiovasc Drugs Ther 21, 69–72 (2007). https://doi.org/10.1007/s10557-007-6008-4

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  • DOI: https://doi.org/10.1007/s10557-007-6008-4

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