Subdepressor dose of benidipine ameliorates diabetic cardiac remodeling accompanied by normalization of upregulated endothelin system in rats

Subrina Jesmin, Yuichi Hattori, Seiji Maeda, Sohel Zaedi, Ichiro Sakuma, Takashi Miyauchi*

*この研究の対応する著者

研究成果: Article査読

15 被引用数 (Scopus)

抄録

We investigated whether benidipine, a long-acting calcium channel blocker (CCB), can normalize cardiac expression profiles of the endothelin (ET)-1 system in insulin-resistant diabetes. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of human Type 2 diabetes, were treated for 12 wk with vehicle or benidipine (3 mg·kg-1·day-1). OLETF rats exhibited a significant increase in ET-1 in plasma and left ventricular (LV) tissues compared with nondiabetic controls. Expression of prepro-ET-1, ET-converting enzyme, and ETA and ETB receptors in LV tissues was also significantly higher in OLETF rats. The two MAPKs, JNK and p38MAPK, both of which are activated by ET-1, were more abundantly expressed in OLETF rat LV tissues. All these alterations were reversed to nondiabetic levels when OLETF rats were treated with the subdepressor dose of benidipine. Furthermore, benidipine therapy resulted in hindering cardiomyocyte hypertrophy and cardiac perivascular fibrosis in OLETF rats. The beneficial actions of benidipine at the subdepressor dose on cardiac remodeling in insulin-resistant diabetes may involve normalization of the upregulated ET-1 system.

本文言語English
ページ(範囲)H2146-H2154
ジャーナルAmerican Journal of Physiology - Heart and Circulatory Physiology
290
5
DOI
出版ステータスPublished - 2006 5
外部発表はい

ASJC Scopus subject areas

  • 生理学
  • 循環器および心血管医学
  • 生理学(医学)

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