- 作者：Alicja Tomaszek ; Liliana Kiczak ; Jacek Bania ; Pawe? Krupa ; Urszula Pas?awska ; Maciej Zacharski ; Adrian Janiszewski ; Tadeusz Stefaniak ; Dorota Zy?ko ; Hossein Ardehali ; Ewa A. Jankowska ; Piotr Ponikowski
- 关键词：Parasympathetic system ; Medulla oblongata ; Tachyarrhythmic experimental model of heart failure ; ¦Á7 acetylcholine nicotinic receptor ; Acetylcholinesterase ; Choline acetyltransferase ; Pigs
- 刊名：Autonomic Neuroscience
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：177
- 期：2
- 页码：253-259
- 全文大小：566 K
Background
Autonomic imbalance constituting a fundamental feature of heart failure (HF) has been assessed mainly at the periphery. Changes in the functioning of autonomic centers in the brain remain unclear. We investigated the molecular elements of parasympathetic system, i.e. ¦Á7 nicotinic acetylcholine receptor (¦Á7nAChR) and enzymes metabolizing acetylcholine (acetylcholinesterase, AChE, choline acetyltransferase, ChAT) in medulla oblongata (MO) of male pigs with chronic tachycardia-induced cardiomyopathy.Methods
The mRNA levels of AChE, ChAT, ¦Á7nAChR and X-box binding protein 1 (spliced form, XBP1s) in MO were analyzed using qPCR, AChE and ChAT activities using spectrophotometry, proteasome activity using fluorometry, and the protein level of ¦Á7nAChR using Western blotting.
Results
The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and ¦Á7nAChR mRNA in MO, an increase in AChE activity (all p < 0.05), and no change in either the mRNA or activity of ChAT. Both circulating catecholamine levels and AChE activity were inversely related to systolic function of left myocardial ventricle (p < 0.05). The level of ¦Á7nAChR protein in MO and its cytoplasmatic fraction were higher in pigs with moderate and severe HF as compared to the other animals (p < 0.01). There was no difference in proteasome activity in MO between diseased and healthy animals, whereas the XBP1s mRNA decreased during HF progression (p < 0.05).
Conclusions
Molecular elements of parasympathetic system are changed within the medulla oblongata during the progression of systolic non-ischemic heart failure in male pigs, indicating a functional link between MO and heart in HF.