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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
- Source :
- Exp Ther Med
- Publication Year :
- 2020
- Publisher :
- Spandidos Publications, 2020.
-
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.
- Subjects :
- Cardioprotection
Cancer Research
AMPK
Articles
General Medicine
Pharmacology
Nicotinic acetylcholine receptor
chemistry.chemical_compound
Immunology and Microbiology (miscellaneous)
chemistry
Muscarinic acetylcholine receptor
medicine
Cholinergic
Hexamethonium
Acetylcholine
medicine.drug
Acetylcholine receptor
Subjects
Details
- ISSN :
- 17921015 and 17920981
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Experimental and Therapeutic Medicine
- Accession number :
- edsair.doi.dedup.....6cab31be35dac0149b9cb734f5768a58