Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and triggered by p38 MAP kinase and Erk1/2.

We previously reported that acute intermittent hypoxia (IH) confers delayed cardioprotection against a prolonged ischemic insult in the rat, via the involvement of nitric oxide synthase and K(ATP) channels. In the present study, we investigated the role of protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), stress activated p38 MAP kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2) using selective inhibitors of these pathways. Adult male rats were exposed to 1-min cycles of IH (10% O(2), 40 s)/normoxia (21% O(2), 20 s) during 4 h or to normoxic cycles. 24 h later, isolated hearts were perfused in Langendorff mode and subjected to a 30-min global ischemia followed by 120 min of reperfusion. Compared to normoxic conditions, IH significantly reduced infarct size (22.2+/-2.4% vs. 33.8+/-2.6%, p