Vagus nerve activation may have important therapeutic significance for
myocardial ischemia-reperfusion (IR) injury.
Nitric oxide (NO) plays a vital role in the cardioprotective effects of
anesthetic preconditioning (APC). Moreover,
acetylcholine (ACh) prevents cardiomyocyte damage by activating
AMP-activated protein kinase (AMPK) and increasing the phosphorylation of Ca2+/
calmodulin-dependent protein kinase β (CaMKKβ). The aim of the present study was to determine whether APC could protect heart function by antagonizing IR damage via the
cholinergic system. It was hypothesized that the
NO synthase (NOS)/CaMKKβ/AMPK pathway might be involved in the cardioprotective effects induced by
cholinergic receptor activation. Isolated rat hearts were subjected to
ischemia for 30 min followed by 120 min of reperfusion. Volatile
anesthetic sevoflurane (3.5%) was administered for 15 min before
ischemia, then rinsed for 15 min. The
muscarinic acetylcholine receptor (mAChR) antagonist
atropine (ATR; 100 nM) and the
nicotinic acetylcholine receptor (nAChR) antagonist
hexamethonium (HEM; 50 µM) were administered 10 min before APC. Both mAChR and nAChR were involved in APC-induced cardioprotection. ATR and HEM treatment both abolished the protective effects of APC on IR damage in isolated hearts, demonstrating the importance of
cholinergic receptors in the protection mechanism of APC. The present study thus suggests that APC plays a cardioprotective role, in part, by regulating neurohumoral pathways. In addition, there may be functional coupling between the two
cholinergic receptors, and the NOS and CaMKKβ/AMPK pathways may play roles in shared pathways that mediate the cardioprotective effects of APC. These findings may provide insight into potential new mechanisms of APC-induced cardioprotection against IR injury.