HYPERTENSION AND THE BRAIN (R WAINFORD, SECTION EDITOR) Vasopressin, Central Autonomic Control and Blood Pressure Regulation Maja Lozić 1 & Olivera Šarenac 1 & David Murphy 2 & Nina Japundžić-Žigon 1 # Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Purpose of Review We present recent advances in understanding of the role of vasopressin as a neurotransmitter in autonomic nervous system control of the circulation, emphasizing hypothalamic mechanisms in the paraventricular nucleus (PVN) involved in controlling sympathetic outflow toward the cardiovascular system. Recent Findings Suggest that somato-dendritically released vasopressin modulates the activity of magnocellular neurons in the PVN and SON, their discharge pattern and systemic release. Advances have been made in uncovering autocrine and paracrine mechanisms controlling presympathetic neuron activity, involving intranuclear receptors, co-released neuroactive substances and glia. Summary It is now obvious that intranuclear release of vasopressin and the co-release of neuroactive substances in the PVN, as well as the level of expression of vasopressin receptors, modulate sympathetic outflow to the cardiovascular system and determine vulnerability to stress. Further research involving patho-physiological models is needed to validate these targets and foster the development of more efficient treatment. Keywords Vasopressin . Blood pressure . Autonomic control . Paraventricular nucleus . Magnocellular neurons . Somato-dendritic release Introduction Cardiovascular diseases are the most frequent cause of morbidity and mortality in the world [ 1]. Given the complex etiology and pathogenesis, partially effective treatment and disconcerting global epidemiological data, there is still a need for better com- prehension of the mechanisms whose failure lead to cardiovas- cular deregulation. But, is the ‘road to Damascus’, when it comes to effective treatment of cardiovascular disorders paved with the necessity to firstly understand the basic mechanisms that regulate normal functioning of cardiovascular system? From the stand- point of new drug discovery it is. Vasopressin is one of the key mechanisms in cardiovascu- lar control. It was discovered more than a century ago, its physiological roles have been well defined but its contribution to the pathogenesis of cardiovascular diseases is still elusive. Vasopressin is a nonapeptide, mostly synthesized in the supra- optic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus, wherefrom it acts both as hormone and neuro- transmitter. At the periphery it is a key contributor to hydromineral homeostasis and is a most potent vasoconstric- tor. Centrally vasopressin mediates many tasks; it is a power- ful modulator of the stress response, vital autonomic functions (cardio-respiratory and body temperature regulation), behav- ior, memory etc. [2]. This paper focuses on recent advances in understanding the role of vasopressin as neurotransmitter in autonomic nervous system control of the circulation. Evidence given over the last 5 years has elucidated central hypothalamic mechanisms in the PVN by which vasopressin, as a neurotransmitter, contributes to increased sympathetic outflow. Central Autonomic Control of Blood Pressure Blood pressure is a vital function that supplies blood flow, oxygen and nutrients to organs. It is fine-tuned by changes Maja Lozić and Olivera Šarenac contributed equally to this work. This article is part of the Topical Collection on Hypertension and the Brain * Nina Japundžić-Žigon nina.zigon@med.bg.ac.rs; nina.japundzic@gmail.com 1 Laboratory for Cardiovascular Pharmacology, Institute of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Dr Subotica 1, Belgrade 11000, Serbia 2 Molecular Neuroendocrinology Research Group, The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK Current Hypertension Reports (2018) 20:11 https://doi.org/10.1007/s11906-018-0811-0