(A) Cardiac functional performance measured and represented as left RPP in rat hearts pre-treated with control (saline treated), OR-B plus OX1R antagonist, OX1R antagonist alone, OR-B plus wortmannin (wort; a PI3K inhibitor) and wortmannin alone (*P<0.05 compared with control). (B) LV infarct size determination (%LV) in pre-treated hearts with OR-B plus OX1R antagonist, OX1R antagonist alone, OR-B plus wortmannin and wortmannin alone (***P<0.001 compared with control). Dotted line across denotes control levels. (C) OR-B time-dependent treatment and Akt phosphorylation: exposure of rat cardiomyocytes to OR-B (100 nM) induced maximal phosphorylation at 5 min. Change in the phosphorylation was evident as early as 2 min post-treatment (*P<0.05, ***P<0.001 compared with basal). (D) OR-B induced a dose-dependent induction in the phosphorylation status of Akt, becoming significant at 1 nM and reaching a plateau at 100 nM (**P<0.01, ***P<0.001 compared with basal). (E) OR-B treatment increased the phosphorylation of ERK1/2 compared with basal levels (***P<0.001). Isoproterenol (ISO) and Angiotensin-II (Angio-II) were employed as positive controls. (F) Inhibition of the MAPK pathway using a selective MAPK inhibitor (U0126) abrogates the protective effect of OR-B on LV infarct size (*P<0.05, **P<0.01, ***P<0.001 compared with control; ^aP<0.05 compared with OR-B).