Adenosine A1 receptor mediates late preconditioning via activation of PKC-δ signaling pathway

Mitsuhiro Kudo, Yigang Wang, Meifeng Xu, Ahmar Ayub, Muhammad Ashraf

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Protein kinase C (PKC) plays a central role in both early and late preconditioning (PC) but its association with inducible nitric oxide synthase (iNOS) is not clear in late PC. This study investigates the PKC signaling pathway in the late PC induced by activation of adenosine A1 receptor (A1R) with adenosine agonist 2-chloro-N6-cyclopentyladenosine (CCPA) and the effect on iNOS upregulation. Adult male mice were pretreated with saline or CCPA (100 μg/kg iv) or CCPA (100 μg/kg iv) with PKC-δ inhibitor rottlerin (50 μg/kg ip). Twenty-four hours later, the hearts were isolated and perfused in the Langendorff mode. Hearts were subjected to 40 min of ischemia, followed by 30 min reperfusion. After ischemia, the left ventricular end-diastolic pressure (LVEDP) was significantly improved and the rate-pressure product (RPP) was significantly higher in the CCPA group compared with the ischemia-reperfusion (I/R) control group. Creatine kinase release and infarct size were significantly lower in the CCPA group compared with the I/R control group. These salutary effects of CCPA were abolished in hearts pretreated with rottlerin. Immunoblotting of PKC showed that PKC-δ was upregulated (150.0 ± 11.4% of control group) whereas other PKC isoforms remained unchanged, and iNOS was also significantly increased (146.2 ± 9.0%, P < 0.05 vs. control group) after 24 h of treatment with CCPA. The data show that PKC is an important component of PC with adenosine agonist. It is concluded that activation of A1R induces late PC via PKC-δ and iNOS signaling pathways.

Original languageEnglish (US)
Pages (from-to)H296-H301
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 52-1
StatePublished - 2002
Externally publishedYes


  • Ischemia
  • Myocardial infarction
  • Nitric oxide

ASJC Scopus subject areas

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


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