The nucleus tractus solitarius (NTS) is the major integrative center within the brainstem for cardiovascular homeostasis. The NTS receives primary input from a variety of cardiovascular afferents such as arterial and cardiopulmonary baroreceptors, peripheral chemoreceptors, somatic and visceral afferents. This information is integrated and via projections to the rostral and caudal ventro-lateral medulla (controlling efferent sympathetic activity) and to the ambiguous complex (controlling efferent parasympathetic activity), reflex control of autonomic nerve activity occurs. Integration of primary afferent information in the NTS can also be markedly affected by descending projections from higher central structures such as specific nuclei within the hypothalamus which have reciprocal connections with the NTS. The NTS neurons contain a rich vocabulary of neurotransmitters and neuromodulators which may affect NTS integration and therefore control of the cardiovascular system. Recently, we and others have shown that adenosine markedly affects NTS integration and thus can elicit profound changes in cardiovascular control. Adenosine levels in the NTS can rise via at least two distinct mechanisms, 1) during cerebral ischemia as occurs, for example, during marked hypotensive hemorrhage or high gravitational stress, and 2) via the breakdown of ATP released as a neurotransmitter or co-transmitter. Adenosine, acting pre-synaptically via both A1 or A2a receptors can modulate the extent of neurotransmitter release. Our previous studies strongly support the concept that different neurotransmitters/neuromodulators operating in the NTS are distinctly linked to specific patterns of regional cardiovascular and sympathetic responses archetypal for specific physiological and pathological situations. A key observation is the unique role of adenosine in the activation of pre-ganglionic adrenal sympathetic nerve activity which innervates the adrenal medulla. NTS adenosine receptor mediated activation of the adrenal medulla likely aids in the restoration of homeostasis during stress as well as likely contributes to the distinct cardiovascular patterns of the defense response. This competing renewal application is focused on 1) determining the mechanisms mediating the responses to stimulation of NTS adenosine receptor subtypes and 2) the role of adenosine receptors in the NTS in modulating cardiovascular responses from descending pathways and ascending peripheral inputs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL067814-07
Application #
7591033
Study Section
Special Emphasis Panel (ZRG1-CVS-B (02))
Program Officer
Thrasher, Terry N
Project Start
2007-04-01
Project End
2011-03-31
Budget Start
2009-04-01
Budget End
2010-03-31
Support Year
7
Fiscal Year
2009
Total Cost
$376,250
Indirect Cost
Name
Wayne State University
Department
Physiology
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J (2015) NTS adenosine A2a receptors inhibit the cardiopulmonary chemoreflex control of regional sympathetic outputs via a GABAergic mechanism. Am J Physiol Heart Circ Physiol 309:H185-97
Minic, Zeljka; O'Leary, Donal S; Scislo, Tadeusz J (2014) Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs. Auton Neurosci 180:32-42
Minic, Zeljka; Li, Cailian; O'Leary, Donal S et al. (2014) Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors. Am J Physiol Heart Circ Physiol 307:H904-9
Ichinose, Tomoko K; Minic, Zeljka; Li, Cailian et al. (2012) Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex. Am J Physiol Regul Integr Comp Physiol 303:R539-50
Mueller, Patrick J; Mischel, Nicholas A; Scislo, Tadeusz J (2011) Differential activation of adrenal, renal, and lumbar sympathetic nerves following stimulation of the rostral ventrolateral medulla of the rat. Am J Physiol Regul Integr Comp Physiol 300:R1230-40
McClure, Joseph M; O'Leary, Donal S; Scislo, Tadeusz J (2011) Neural and humoral control of regional vascular beds via A1 adenosine receptors located in the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 300:R744-55
McClure, Joseph M; Rossi, Noreen F; Chen, Haiping et al. (2009) Vasopressin is a major vasoconstrictor involved in hindlimb vascular responses to stimulation of adenosine A(1) receptors in the nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 297:H1661-72
Scislo, Tadeusz J; Ichinose, Tomoko K; O'Leary, Donal S (2008) Stimulation of NTS A1 adenosine receptors differentially resets baroreflex control of regional sympathetic outputs. Am J Physiol Heart Circ Physiol 294:H172-82
Kitchen, Amy M; O'Leary, Donal S; Scislo, Tadeusz J (2006) Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors. Am J Physiol Heart Circ Physiol 290:H807-12
Scislo, Tadeusz J; O'Leary, Donal S (2006) Adenosine receptors located in the NTS contribute to renal sympathoinhibition during hypotensive phase of severe hemorrhage in anesthetized rats. Am J Physiol Heart Circ Physiol 291:H2453-61

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