Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning

Xian Liang Tang, Eitaro Kodani, Hitoshi Takano, Michael Hill, Ken Shinmura, Thomas M. Vondriska, Peipei Ping, Roberto Bolli

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Although protein tyrosine kinases (PTKs) signaling has been implicated in the late phase of ischemic preconditioning (PC), it is unknown whether PTK signaling is necessary for the development of nitric oxide (NO) donor-induced late PC. Thus conscious rabbits underwent a sequence of six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles followed by a 5-h recovery period of reperfusion for 3 consecutive days (days 1, 2, and 3). On day 0 (24 h before the 6 O/R cycles on day 1), rabbits received no treatment (control), the NO donor diethylenetriamine (DETA)/NO (DETA/NO), the PTK inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), or DETA/NO plus PP2 (DETA/NO + PP2). In control rabbits (n = 6), the six O/R cycles on day 1 resulted in delayed functional recovery, indicating severe myocardial stunning. In rabbits pretreated with DETA/NO (n = 5) on day 1, myocardial stunning caused by the six O/R cycles on day I was markedly attenuated, with a significant reduction (-60%) in the total deficit of wall thickening (WTh) compared with controls, indicating that DETA/NO induced a late PC effect against stunning. However, in rabbits pretreated with DETA/NO + PP2 (n = 5), the total deficit of WTh was significantly greater than that in rabbits treated with DETA/NO alone and was similar to that in controls, indicating that PP2 prevented the development of DETA/NO-induced late PC. In rabbits pretreated with PP2 on day 0 (n = 4), the total deficit of WTh was similar to that in controls, indicating that PP2 does not affect myocardial stunning in itself. We conclude that a PTK-dependent signaling mechanism is necessary for the development of NO donor-induced late PC against myocardial stunning in conscious rabbits.

本文言語English
ページ(範囲)H1441-H1448
ジャーナルAmerican Journal of Physiology - Heart and Circulatory Physiology
284
4 53-4
DOI
出版ステータスPublished - 2003 4月 1
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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