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Comparison of anti-anginal effect of cilnidipine with those of nicardipine and nifedipine in the vasopressin-induced angina model of rats

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Abstract

We assessed the anti-anginal effects of cilnidipine in comparison with those of nicardipine and nifedipine (1 and 10 µg/kg, n = 6 for each drug) or vehicle (n = 6) by using the vasopressin-induced angina model of rats. The administration of vasopressin (0.5 IU/kg, i.v.) to the rats depressed the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it significantly increased the mean blood pressure, resulting in the decrease of the heart rate and the prolongation of the PR interval possibly through a reflex–mediated increase in vagal tone. Cilnidipine suppressed the vasopressin-induced depression of the S-wave level in a dose-related manner, which was not observed by nicardipine or nifedipine. In addition, the low dose of cilnidipine hardly affected the vasopressin-induced pressor response, but it attenuated the negative dromotropic effect, suggesting N-type Ca2+ channel inhibition by cilnidipine might have suppressed the parasympathetic nerve activity in vivo like those reported in the sympathetic nerve. Thus, cilnidipine may become a useful strategy for inhibiting coronary vasospasm-induced anginal attack.

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Acknowledgments

This study was supported in part by the Project Research Grant of Toho University School of Medicine (No. 27-20), JSPS KAKENHI (#25460344), MEXT KAKENHI (#S1101016) and AMED Grant (#AS2116907E). We thank Dr. Suchitra Matsukura, Ms. Misako Nakatani and Mrs. Yuri Ichikawa for their technical assistance.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan

    Xin Cao, Yuji Nakamura, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando & Atsushi Sugiyama

  2. Key Laboratory of Acupuncture and Medicine Research of Ministry Education, Nanjing University of Chinese Medicine, 138 Xianlin Ave, Qixia, Nanjing, Jiangsu, China

    Bingmei Zhu & Bin Xu

  3. Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba, 274-8510, Japan

    Akira Takahara

  4. Yamanashi Research Center of Clinical Pharmacology, 73-5 Hatta, Isawa-cho, Fuefuki, Yamanashi, 406-0023, Japan

    Masaki Saitoh & Atsushi Sugiyama

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  1. Xin Cao
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  2. Yuji Nakamura
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  3. Takeshi Wada
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  4. Hiroko Izumi-Nakaseko
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  6. Bingmei Zhu
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  7. Bin Xu
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  8. Akira Takahara
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  10. Atsushi Sugiyama
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Correspondence to Atsushi Sugiyama.

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Cao, X., Nakamura, Y., Wada, T. et al. Comparison of anti-anginal effect of cilnidipine with those of nicardipine and nifedipine in the vasopressin-induced angina model of rats. Heart Vessels 31, 2045–2052 (2016). https://doi.org/10.1007/s00380-016-0848-4

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  • DOI: https://doi.org/10.1007/s00380-016-0848-4

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