The role of the central nervous system in regulating peripheral haemodynamics has been studied extensively in normotensive and hypertensive subjects but this work has been mostly conducted from a global operational point of view (input-output relationships). Rather little is known about the specific CNS circuits involved. Such well known realities as the sympathetic tone, baroreceptor reflexes, central baroreceptor resetting (drug-induced or otherwise), the """"""""vasomotor center"""""""", have as yet very imprecise neurophysiological substrates. Even the most basic medullary circuits, including the pathways projecting to the sympathetic preganglionic neurons, are very poorly known. The goal of the proposed research is to establish a reasonable model of the medullary pathways involved in controlling the level of the sympathetic outflow and in generating the basal sympathetic tone. Our long-term interest in the pathology of blood pressure regulation is the reason for chosing the rat as experimental subject because of the unique research opportunities presented by the availability of well-studied models of hypertension in this species. The starting point of the proposed investigation is a neurophysiological study of the anterior ventrolateral reticular formation since there is now overwhelming evidence that this area is essential in the maintenance of the sympathetic tone, in the operation of baroreceptor reflexes and in relaying sympathoexcitation due to the activity of higher structures. The proposal is also predicated on our preliminary results which indicate that this area may indeed contain sympathetic premotorneurons (projecting to the thoracic sympathetic nucleus) controling the sympathetic outflow to the vasculature. A large part of the work will therefore be devoted to understanding the role of these neurons in generating the sympathetic tone and their contribution to baroreceptor and other sympathetic reflexes. The nature of the neurotransmitters used by these cells will also be investigated. A second part of the study will be devoted to the afferent inputs of these cells and more particularly to those which convey their powerful baroreceptor inhibition. Finally, an attempt will be made to understand in neurophysiological terms the pathology of a model of human essential hypertension, the SHR rat. This work represents an extension of our previous research which was more specifically targeted toward understanding the role of central monoaminergic pathways in central autonomic regulations.
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