Ischaemic and Pharmacological Preconditioning Is Associated with Attenuation of p38 MAPK Activation During Sustained Ischaemia and Reperfusion

Abstract

The stress kinase, p38 mitogen activated protein kinase (p38 MAPK), is known to be activated by both ischaemia and reperfusion. Whether this activation is beneficial or deleterious is still a matter of debate. The aims of this study were to (i) evaluate the activation pattern of p38 MAPK during a multi-cycle preconditioning protocol, during sustained (index) ischaemia and during reperfusion (ii) use transient β-adrenergic stimulation to mimic ischaemic preconditioning and to study its effects on p38 MAPK activation and (iii) reevaluate the effects of p38 MAPK blockade by SB 203580 on cardioprotection elicited by ischaemic preconditioning as well as by β-adrenergic preconditioning. The isolated perfused working rat heart was subjected to a preconditioning protocol of 3 X 5 min global ischaemia or 5 min isoproterenol (10-7M) followed by 5 min washout. All hearts were then subjected to 25 min global ischaemia and 30 min reperfusion during which time mechanical function was monitored. Hearts were freeze-clamped at different time intervals for subsequent analysis of p38 MAPK activation using Western blotting and a p38 MAPK phospho-antibody (Thr 180/Tyr 182).