AMP-activated protein kinase (AMPK) protects various tissues and cells from ischemic insults and is activated by many stimuli including mechanical stretch. Therefore, this study investigated if the activation of AMPK is involved in stretch-induced cardioprotection (SIC). Intraventricular balloon and aorto-caval shunt (ACS) were used to stretch rat hearts ex vivo and in vivo, respectively. Stretch preconditioning reduced
myocardial infarct induced by
ischemia-reperfusion (I/R) and improved post-ischemic functional recovery. Phosphorylation of AMPK and its downstream substrate,
acetyl-CoA carboxylase (ACC) were increased by mechanical stretch and ACC phosphorylation was completely blocked by the
AMPK inhibitor, Compound C. AMPK activator (
AICAR) mimicked SIC.
Gadolinium, a blocker of stretch-activated
ion channels (SACs), inhibited the stretch-induced phosphorylation of AMPK and ACC, whereas
diltiazem, a specific
L-type calcium channel blocker, did not affect AMPK activation. Furthermore, SIC was abrogated by Compound C and
gadolinium. The in vivo stretch induced by ACS increased AMPK activation and reduced
myocardial infarct. These findings indicate that stretch preconditioning can induce the cardioprotection against I/R injury, and activation of AMPK plays an important role in SIC, which might be mediated by SACs.