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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028785-10
Application #
3340072
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1989-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Stornetta, Ruth L; Guyenet, Patrice G (2018) C1 neurons: a nodal point for stress? Exp Physiol 103:332-336
Guyenet, Patrice G (2017) Putative Mechanism of Salt-Dependent Neurogenic Hypertension: Cell-Autonomous Activation of Organum Vasculosum Laminae Terminalis Neurons by Hypernatremia. Hypertension 69:20-22
Valentino, Rita J; Guyenet, Patrice; Hou, Xun Helen et al. (2017) Central Network Dynamics Regulating Visceral and Humoral Functions. J Neurosci 37:10848-10854
Abe, Chikara; Inoue, Tsuyoshi; Inglis, Mabel A et al. (2017) C1 neurons mediate a stress-induced anti-inflammatory reflex in mice. Nat Neurosci 20:700-707
Wenker, Ian C; Abe, Chikara; Viar, Kenneth E et al. (2017) Blood Pressure Regulation by the Rostral Ventrolateral Medulla in Conscious Rats: Effects of Hypoxia, Hypercapnia, Baroreceptor Denervation, and Anesthesia. J Neurosci 37:4565-4583
Basting, Tyler M; Abe, Chikara; Viar, Kenneth E et al. (2016) Is plasticity within the retrotrapezoid nucleus responsible for the recovery of the PCO2 set-point after carotid body denervation in rats? J Physiol 594:3371-90
Stornetta, Ruth L; Inglis, M Andrews; Viar, Kenneth E et al. (2016) Afferent and efferent connections of C1 cells with spinal cord or hypothalamic projections in mice. Brain Struct Funct 221:4027-4044
Guyenet, Patrice G; Bayliss, Douglas A; Stornetta, Ruth L et al. (2016) Proton detection and breathing regulation by the retrotrapezoid nucleus. J Physiol 594:1529-51
Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J et al. (2016) Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through ?7nAChR+ splenocytes. J Clin Invest 126:1939-52
Zheng, H; Stornetta, R L; Agassandian, K et al. (2015) Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats. Brain Struct Funct 220:3011-22

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