Autonomic control of the heart: going beyond the classical neurotransmitters

Abstract

What is the topic of this review? This symposium report discusses the evidence for release of cardiac sympathetic cotransmitters in addition to noradrenaline. What advances does it highlight? It highlights the potential role of neuropeptide Y in reducing vagal neurotransmission and directly influencing ventricular myocyte excitability in the presence of β-receptor blockade. Acute myocardial infarction and congestive cardiac failure are characterized by high levels of cardiac sympathetic drive. In these conditions, sympathetic neurotransmitters such as neuropeptide Y (NPY) can be released in addition to noradrenaline, and plasma levels correlate with infarct size and mortality. Even in the presence of β-blockers, NPY is able to bind to its own receptors located on cholinergic ganglia and ventricular myocytes. In this symposium report, I review the evidence that NPY can inhibit acetylcholine release during vagus nerve stimulation and limit the subsequent bradycardia. I also present preliminary, as yet unpublished data, demonstrating that NPY may be pro-arrhythmic by directly influencing ventricular electrophysiology. Targeting NPY receptors pharmacologically may therefore be a useful therapeutic strategy both to reduce heart rate and to prevent arrhythmias in the setting of myocardial infarction and chronic heart failure. Such medications would be expected to act synergistically with β-blockers, angiotensin-converting enzyme inhibitors and implantable cardiac devices, such as defibrillators and vagus nerve stimulators.

Figure 1. Potential actions of the sympathetic cotransmitter neuropeptide Y (NPY, in red)

Although β-blockers (represented by the yellow cross) prevent the action of noradrenaline (NA, in black), high-level sympathetic stimulation also causes the release NPY. Neuropeptide Y can act on Y₂ receptors on cholinergic ganglia to reduce the release of acetylcholine (ACh) and result in vagal bradyacardia via a protein kinase C (PKC)-dependent pathway. Independent of heart rate, NPY may also act on Y₁ receptors on ventricular myocytes to influence their electrophysiology and predispose to ventricular arrhythmias. Adapted with permission from Herring et al. (2012).