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Curr Neuropharmacol. 2011 Jun;9(2):262-77. doi: 10.2174/157015911795596531.

Function and pharmacology of spinally-projecting sympathetic pre-autonomic neurones in the paraventricular nucleus of the hypothalamus.

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1
Centre for Integrative Mammalian Biology, University of Liverpool, Brownlow Hill & Crown St. Liverpool, L69 7ZJ, UK.

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 high-lights 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:

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

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