Age-related attenuation of parasympathetic control of the heart in mice.

The autonomic nervous system maintains homeostasis through the balance of the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS). Especially evident in the heart, maintenance of this balance is important for the control of heart rate, conduction, and contractility. It is known that aging, similar to various cardiovascular diseases, results in an increase in SNS activity and a decrease in PSNS activity, which may contribute to age-related cardiac dysfunction and remodeling. Intracardiac ganglia relay and integrate the PSNS signals to the heart. Therefore, this study investigated whether altered function of intracardiac ganglia is involved in age-related parasympathetic dysfunction and the potential role of the major cholinergic components of intracardiac ganglionic transmission in the process. This study utilized two age groups of mice, the younger mice at 1-2.5 months of age, and the older mice at 11-12 months of age. The results show that the older mice exhibit diminishment of both baroreflex sensitivity and response to rostral-severed vagal stimulation but preserved response to administration of muscarinic acetylcholine receptor agonist, bethanechol. Analysis of whole atrial lysate revealed significant diminishments in choline acetyltransferase (ChAT) and the upper band of vesicular acetylcholine transporter (VAchT). In contrast, the upper band of the high affinity choline transporter (CHT) was significantly upregulated in the older group. Further analysis showed that the soluble but not insoluble fraction of CHT protein is significantly increased in the older group. This implicates a potential reduction of acetylcholine synthesis and/or release and an improper compensatory change of CHT may be responsible for the PSNS dysfunction exhibited in this model.