Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure

Abstract

Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure. Am J Physiol Heart Circ Physiol 309: H1281-H1287, 2015. First published September 14, 2015; doi:10.1152/ajpheart.00445.2015.-Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. heart failure; cardiac hypertrophy; parasympathetic; autonomic; vagal NEW & NOTEWORTHYA common hallmark of cardiovascular diseases is autonomic imbalance. Left ventricular hypertrophy altered both excitatory and inhibitory neurotransmission to cardiac vagal neurons that generate parasympathetic activity to the heart. These preferentially altered network pathways and neurotransmitter receptors provide future targets to restore parasympathetic activity in these diseases.HYPERTENSION, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affects nearly 23 million people worldwide with ϳ2 million new patients diagnosed annually (15). Cardiac rhythm disturbances lead to sudden cardiac death in 40 -50% of advanced HF patients with a 1-yr mortality rate of Ͼ50% (10). A distinctive hallmark of cardiac hypertrophy, HF, and the accompanying cardiac conduction abnormalities is autonomic imbalance,...

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Long-term stimulation of cardiac vagal preganglionic neurons reduces blood pressure in the spontaneously hypertensive rat

“…However, age-related reduction in the population of DVMN neurons in the SHRs might also be accompanied with abnormalities in DVMN neuronal excitability. Previous studies have shown that parasympathetic neuronal dysfunction is a common feature in animal models of cardiovascular disease such as heart failure and chronic intermittent hypoxia in which increased GABAergic/glycinergic neurotransmission and decreased excitatory neurotransmission in the DVMN and nucleus ambiguous result in reduced neuronal excitability and lower parasympathetic tone (39,40). Similar mechanisms are likely to operate in the SHR and should be further investigated in future studies to help determine whether DVMN synaptic dysfunction, a selective loss of parasympathetic preganglionic neurons supplying the heart or a remodelling of their cardiac projections, might promote abnormal changes in left ventricular inotropy and/or loss of structural integrity in the aortic wall which might contribute to the development of arterial hypertension.…”

A brain within the heart: A review on the intracardiac nervous system

“…Therefore it is not surprising that most of these studies are performed using in vitro preparations of intracardiac neurons, what imposes several limitations to the interpretation of the respective findings. At this level the patch clamp technique has been widely used to understand the plasticity and function of intracardiac neurons [79,85], since it is the gold standard technique to analyze the electrical properties and functional connectivity of neurons. In addition the patch clamp technique offers the advantage to study simultaneously the function, organization and network of the ICNS.…”