Our current understanding of the central nervous system networks involved in the elaboration of the sympathetic vasomotor outflow is still fragmentary. More information is highly desirable for at least two main practical reasons in addition to the basic scientific interest of the subject. One is to ultimately understand the sympathetic dysfunction associated with various forms of hypertension. The second is to clarify the mechanism of action of clinically useful centrally-acting hypotensive agents in order to improve current therapeutic approaches. The present program represents an extension of our previous work on the neuroanatomy and neurophysiology of the medullary circuits involved in generating the vasomotor tone. A major goal of the present proposal is to differentiate the integrative function of two types of efferent vasomotor neurons located in the rostral ventrolateral medulla. These cells are responsible in large part for generating the basal vasomotor tone and are involved in a number of vasomotor reflexes. One type consists of adrenergic cells, the other of neurons with intrinsic pacemaker activity but undetermined transmitter. These studies will be carried out with unit recording """"""""in vivo"""""""" and by intracellular methods in tissue slices. The second half of our effort will be devoted to understand the role of a second portion of the ventrolateral medulla located more caudally around nucleus ambiguous at the level of the obex (the periambigual area, pAa). The importance of this area stems from the fact that it exerts a tonic restraining influence on the vasoconstrictor sympathetic outflow. """"""""In vivo"""""""" electrophysiological techniques and tract-tracing neuroanatomical methods will be used to address such questions as: i) Whether the restraining influence of the pAa is or not driven by peripheral inputs involved in the feedback control of arterial pressure. ii) What are the exact location, properties and neurotransmitter content of the pAa neurons involved in vasomotor control. iii) What are the synaptic interactions between the pAa and the rostral ventrolateral medullary afferent vasomotor neurons.
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