Parasympathetic Nervous System and Heart Failure: Pathophysiology and Potential Implications for Therapy

Abstract

A bundant evidence links sympathetic nervous system activation to outcomes of patients with heart failure (HF). 1 In contrast, parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized.][4][5] In the present article, we review cardiovascular responses to parasympathetic activation, address the modulating factors that can affect parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the parasympathetic nervous system may have important therapeutic implications for patients with congestive HF. Structure of the Parasympathetic Limb of the Autonomic Nervous SystemThe parasympathetic nervous system originates from medial medullary sites (nucleus ambiguous, nucleus tractus solitarius, and dorsal motor nucleus) and is modulated by the hypothalamus.Vagal efferents extend from the medulla to postganglionic nerves that innervate the atria via ganglia located in cardiac fat pads with neurotransmission that is modulated via nicotinic receptors.Postganglionic parasympathetic and sympathetic cholinergic nerves then affect cardiac muscarinic receptors (the Figure ). 6 -8 Vagus nerve afferent activation, originating peripherally, can modulate efferent sympathetic and parasympathetic function centrally and at the level of the baroreceptor.Efferent vagus nerve activation can have tonic and basal effects that inhibit sympathetic activation and release of norepinephrine at the presynaptic level.Acetylcholine release from parasympathetic nerve terminals will activate ganglionic nicotinic receptors that in turn activate muscarinic receptors at the cellular level.Cardiovascular effects include heart rate reduction by inhibition of the sympathetic nervous system and by direct hyperpolarization of sinus nodal cells.Parasympathetic activation can affect atrioventricular nodal conduction mediated predominantly through the left vagus nerve.Furthermore, muscarinic receptors on blood vessel walls can cause vasorelaxation through a nitric oxide (NO)-modulated pathway but can also cause vasoconstriction by directly activating smooth muscle. 6 -8 Therefore, although the sympathetic nervous system has global effects on cardiovascular physiology in an all-or-none type of response, the parasympathetic nervous system can have selective modulation at various levels.