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Current Neuropharmacology

Eiditor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Function and Pharmacology of Spinally-Projecting Sympathetic Pre-Autonomic Neurones in the Paraventricular Nucleus of the Hypothalamus

Author(s): Richard Barrett-Jolley, Nicolas Nunn, Matthew Womack and Caroline Dart

Volume 9 , Issue 2 , 2011

Page: [262 - 277] Pages: 16

DOI: 10.2174/157015911795596531

Price: $58

Abstract

The paraventricular nucleus (PVN) of the hypothalamus has been described as the “autonomic master controller”. It co-ordinates critical physiological responses through control of the hypothalamic-pituitary-adrenal (HPA)-axis, and by modulation of the sympathetic and parasympathetic branches of the central nervous system. The PVN comprises several anatomical subdivisions, including the parvocellular/ mediocellular subdivision, which contains neurones projecting to the medulla and spinal cord. Consensus indicates that output from spinally-projecting sympathetic pre-autonomic neurones (SPANs) increases blood pressure and heart rate, and dysfunction of these neurones has been directly linked to elevated sympathetic activity during heart failure. The influence of spinally-projecting SPANs on cardiovascular function highlights their potential as targets for future therapeutic drug development. Recent studies have demonstrated pharmacological control of these spinally-projecting SPANs with glutamate, GABA, nitric oxide, neuroactive steroids and a number of neuropeptides (including angiotensin, substance P, and corticotrophin-releasing factor). The underlying mechanism of control appears to be a state of tonic inhibition by GABA, which is then strengthened or relieved by the action of other modulators. The physiological function of spinally-projecting SPANs has been subject to some debate, and they may be involved in physiological stress responses, blood volume regulation, glucose regulation, thermoregulation and/or circadian rhythms. This review describes the pharmacology of PVN spinally-projecting SPANs and discusses their likely roles in cardiovascular control.

Keywords: pharmacology, angiotensin, vasopressin, tachykinin, substance P, oxytocin, neuropeptides, parvocellular mediocellular, sympathetic, cardiovascular, hypothalamus, paraventricular nucleus, PVN, GABA, penile erection, Blood pressure


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