The Chromogranin A-derived anti-hypertensive peptide catestatin (CST) exerts cardioprotective effects by inhibiting catecholamine release and reducing cardiac contractility. We have recently reported that CST reduces ischemia/reperfusion (I/R) injury and improves cardiac performance when administered at the onset of reperfusion (R), reducing post-ischemic rise of left ventricular (LV) diastolic pressure and enhancing the recovery of developed LVP. At present, the mechanisms underlying the cardioprotective effect of CST are not known. Therefore, we investigated whether reperfusion injury salvage kinases (RISK) activation contributes to the protective effect of this peptide.

Methods 

Isolated rat hearts perfused at constant flow were subjected to 30 min ischemia (I) and 120 min R (I/R group), or treated with 75 nM CST during the first 20 min of R (CST-R group). Besides contractile performance during R, we assessed infarct size (IS) and phosphorylation of kinases (by western blotting) at the end of R. Results. IS, which was about 60% of risk area in I/R group hearts, was reduced to about 35% in CST-R group (p<0.05). Concomitant with the improvement of post-ischemic recovery of developed LVP, CST enhanced the level of phospho-Akt, ERK 1/2, and GSK3b. These findings suggest that the phosphorylation/activation of several protective kinases may contribute to the CST-induced cardioprotective effects.