Diminished Excitatory Neurotransmission To Brainstem Cardiac Vagal Neurons In Rats With Ascending Aortic Constriction‐Induced Heart Failure

Abstract

An imbalance in autonomic activity to the heart, increased sympathetic activation and reduced parasympathetic tone, are important pathophysiological contributors to the progression of heart failure (HF), and are associated with poor outcome in patients. However the mechanisms responsible for reduced parasympathetic activity to the heart in HF is unknown. Cardiac parasympathetic activity originates from cardiac vagal neurons (CVNs) located in the brainstem. In this study we test the hypothesis that activation of CVNs is altered in an animal model of HF. HF was established by ascending aortic banding (AAB), by banding the ascending aorta with a 3‐0 silk suture ligature tied against a 0.8mm blunt steel wire. The wire was removed, whereby the aorta was constricted to 60–70% of the original diameter. Aged‐matched control animals underwent a right thoracotomy and the ascending aorta was isolated but not constricted. After five weeks the spontaneous excitatory postsynaptic currents (EPSCs) in CVNs were significantly decreased in AAB animals. The frequency of EPSCs were diminished from an average of 3.8 ± 0.8 Hz (in control) to 0.9 ± 0.1 Hz (AAB) and the EPSCs amplitude reduced from 31.8 ± 2.6 pA (control) to 26 ± 2.1 pA (AAB). This diminished frequency and amplitude of EPSCs in CVNs would result in a decrease of parasympathetic activity to the heart, and is likely a mechanism for autonomic dysfunction that occurs in heart failure.