Protein Kinase A as Another Mediator of Ischemic Preconditioning Independent of Protein Kinase C

• DOI: 10.1161/01.cir.0000133390.12306.c7
• Publication Date: 2004-06-22T00:14:33Z
• Authors: Shoji Sanada; Hiroshi Asanuma; Osamu Tsukamoto; Tetsuo Minamino; Koichi Node; Seiji Takashima; Tomi Fukushima; Akiko Ogai; Yoshiro Shinozaki; Masashi Fujita; Akio Hirata; Hiroko Okuda; Hiroaki Shimokawa; Hitonobu Tomoike; Masatsugu Hori; Masafumi Kitakaze
• Keywords: Ischemic Preconditioning

We and others have reported that transient accumulation of cyclic AMP (cAMP) in the myocardium during ischemic preconditioning (IP) limits infarct size independent protein kinase C (PKC). Accumulation cAMP activates A (PKA), which has been demonstrated to cause reversible inhibition RhoA Rho-kinase. investigated involvement PKA Rho-kinase limitation by IP.Dogs were subjected 90-minute ischemia 6-hour reperfusion. examined effect on activity sustained (1) preischemic coronary occlusion (IP), (2) activation PKA/PKC, (3) PKA/PKC IP, (4) or actin cytoskeletal deactivation myocardial ischemia. Either IP dibutyryl-cAMP treatment activated PKA, was dose-dependently inhibited 2 inhibitors (H89 Rp-cAMP). substantially reduced size, blunted inhibition. activation, but not PKC caused a substantial decrease These changes cancelled PKC. Furthermore, either (hydroxyfasudil Y27632) (cytochalasin-D) achieved same as without affecting systemic hemodynamic parameters, area at risk, collateral blood flow.Transient reduces through ischemia, implicating novel mechanism for cardioprotection potential new therapeutic target.