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      Cholinergic receptors play a role in the cardioprotective effects of anesthetic preconditioning: Roles of nitric oxide and the CaMKKβ/AMPK pathway

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          Abstract

          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 Ca 2+/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.

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          Author and article information

          Journal
          Exp Ther Med
          Exp Ther Med
          ETM
          Experimental and Therapeutic Medicine
          D.A. Spandidos
          1792-0981
          1792-1015
          February 2021
          14 December 2020
          14 December 2020
          : 21
          : 2
          Affiliations
          [1 ]Department of Anesthesiology, Wujiang Hospital Affiliated to Nantong University, Suzhou, Jiangsu 215200, P.R. China
          [2 ]Department of Cardiology, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China
          [3 ]Institute of Clinical Medicine Research, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China
          [4 ]Department of Anesthesiology and Perioperative Medicine, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China
          Author notes
          Correspondence to: Professor Jianzhong An, Institute of Clinical Medicine Research, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, 1 Lijiang Road, Gaoxin, Suzhou, Jiangsu 215153, P.R. China szkjcyy_ajz@ 123456126.com

          *Contributed equally

          Article
          PMC7791965 PMC7791965 7791965 ETM-0-0-09569
          10.3892/etm.2020.9569
          7791965
          33456504
          Copyright © 2020, Spandidos Publications
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