Tomaszek_2013_Auton.Neurosci_177_253

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. alpha7 nicotinic acetylcholine receptor (alpha7nAChR) 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, alpha7nAChR 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 alpha7nAChR using Western blotting.
RESULTS: The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and alpha7nAChR 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 alpha7nAChR 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.