Peptidic regulation of heart rate and interactions with the autonomic nervous system

Autonomic influences on the heart rate have been the subject of intense research for many decades and are classically devoted to the sympathetic and parasympathetic systems. However, developments over the past few years in our knowledge of the organization of the autonomic nervous system have led to the conclusion that in addition to the classical transmitters, peptidic transmitters are clearly present and have direct or indirect actions on cardiac conduction. Neuropeptides have been found to collocate with each other or with classical transmitters, thereby increasing the variety of chemical signals that a neuron can utilize to communicate with other cells. Neuropeptides can act as neurotransmitters, neuromodulators or neurohormones. Some are produced in endocrine glands and circulate as hormones, while others are contained in cardiac myocytes, neurons, or endothelial cells in proximity to the sinoatrial node and can therefore act in a paracrine or autocrine way on the pacemaker cells to modulate heart frequency. There is evidence supporting such a role, especially for locally situated neuropeptide Y, vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, angiotensin II, natriuretic peptides, endothelins and possibly many others. The role of the peptidic neurotransmitters in the conduction system should not be exaggerated. Nevertheless, neuropeptides certainly represent a new category of neurotransmitters forming a third component of the autonomic nervous system and may have complex actions with potential therapeutic implications in man.