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

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15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)H1441-H1448
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number4 53-4
Publication statusPublished - 2003 Apr 1

Keywords

  • Diethylenetriamine/nitric oxide
  • Ischemia-reperfusion injury
  • Rabbit
  • pp2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Tang, X. L., Kodani, E., Takano, H., Hill, M., Shinmura, K., Vondriska, T. M., Ping, P., & Bolli, R. (2003). Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning. American Journal of Physiology - Heart and Circulatory Physiology, 284(4 53-4), H1441-H1448.