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Effects of masitinib compared with tadalafil for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats
https://repository.lib.tottori-u.ac.jp/records/7392
https://repository.lib.tottori-u.ac.jp/records/7392bddddedb-7dd2-47c3-b622-789d0275c902
| 名前 / ファイル | ライセンス | アクション |
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vp122_j_vph_2019_106599.pdf (8.9 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2022-09-08 | |||||
| タイトル | ||||||
| タイトル | Effects of masitinib compared with tadalafil for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題 | Cardiopulmonary remodeling | |||||
| キーワード | ||||||
| 主題 | Masitinib | |||||
| キーワード | ||||||
| 主題 | Pulmonary arterial hypertension | |||||
| キーワード | ||||||
| 主題 | Right ventricular hypertrophy | |||||
| キーワード | ||||||
| 主題 | Tadalafil | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | Cardiopulmonary remodeling | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | Masitinib | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | Pulmonary arterial hypertension | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | Right ventricular hypertrophy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | Tadalafil | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
日笠, 喜朗
× 日笠, 喜朗× Leong, Zi Ping |
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| 著者所属（英） | ||||||
| 言語 | en | |||||
| 値 | The United Graduate School of Veterinary Science, Yamaguchi University | |||||
| 著者所属（英） | ||||||
| 言語 | en | |||||
| 値 | The United Graduate School of Veterinary Science, Yamaguchi University / Joint Department of Veterinary Medicine, Laboratory of Veterinary Internal Medicine, Faculty of Agriculture, Tottori University | |||||
| 抄録 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Targeting vascular remodeling in pulmonary arterial hypertension (PAH) remains a challenge given the lack of potent anti-remodeling abilities of the therapeutic drugs. Although sildenafil has been shown to ameliorate cardiopulmonary remodeling, that of tadalafil is questionable. Masitinib, a tyrosine kinase inhibitor appears safer and more potent than imatinib for treatment of malignancies, but its efficacy on PAH is unknown. Therefore, we investigated the anti-remodeling properties of masitinib (5, 15, 50 mg/kg) and tadalafil (5, 10 mg/kg) using a monocrotaline-induced rat model of PAH. The 14-day treatment with masitinib (15, 50 mg/kg) resulted in significantly decreased right ventricular (RV) systolic pressure (RVSP) and hypertrophy (RVH), and pulmonary vascular remodeling, whereas tadalafil showed weaker anti-remodeling properties. Besides, masitinib significantly blocked the mitogen-associated protein kinase (MAPK) pathway, and reduced phosphodiesterase (PDE)-5 mRNA expression in the lungs. By contrast, tadalafil did not significantly inhibit the MAPK pathway. Further, the 28-day treatment extension revealed that masitinib-treated rats (15 mg/kg) had significantly lower RVSP, and higher heart rate and serum cyclic guanosine monophosphate (cGMP) level, whereas those treated with tadalafil (10 mg/kg) showed insignificantly lower RVSP and higher cGMP level. Moreover, the RVH indices, heart rates, body weight gains, and survival rates of rats in both groups were comparable. Collectively, these results suggest that the treatment with a low-dose masitinib was non-inferior than tadalafil. A lower dose of masitinib may represent a novel approach to target both the cardiopulmonary remodeling and the dysregulated vasoconstriction in PAH. | |||||
| 書誌情報 |
Vascular Pharmacology en : Vascular Pharmacology 巻 122-123, p. 106599, 発行日 2019-12-31 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 15371891 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.vph.2019.106599 | |||||
| 権利 | ||||||
| 権利情報 | (C) 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
| 情報源 | ||||||
| 関連名称 | Leong, Zi Ping. Hikasa, Yoshiaki. Effects of masitinib compared with tadalafil for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats. Vascular Pharmacology. 122-123. 106599. 2019. doi:10.1016/j.vph.2019.106599 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.sciencedirect.com/science/article/pii/S1537189119301193 | |||||
| 関連名称 | https://www.sciencedirect.com/science/article/pii/S1537189119301193 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
