We have localized immunoreactivity for neuronal nitric oxide synthase, glutamate, NMDAR1 receptor subunits, and GLUR1 receptor subunits in the nucleus tractus solitarii (NTS) of rats and have identified strong associations between glutamate and nNOS and between each of the receptor types and nNOS in NTS. Our pharmacological studies suggest that responses to activation of glutamate receptors in NTS represent integrated action dependent on a link between ionotropic glutamate receptor and nitric oxide mechanisms in the NTS. The current protocols utilize immunohistochemical light, confocal and electron microscopic techniques and pharmacological methods to test the hypothesis that baroreflex transmission through ionotropic glutamate receptors in the nucleus tractus solitarii depends on neuronal nitric oxide synthase and soluble guanylate cyclase. There are two multifaceted specific aims. First we seek to define physiological and anatomical relationships between glutamatergic baroreceptor transmission and nNOS in NTS. Second, we seek to define physiological and anatomical relationships between glutamate receptors and cyclic GMP in NTS. We anticipate these studies will demonstrate that cardiovascular responses elicited by activation of NMDA and non-NMDA ionotropic glutamate receptors in NTS will depend to a significant degree on an intact nitroxidergic system in NTS, that responses will be attenuated or lost with interruption of the latter system, and that baroreflexes will be attenuated by interruption of nitric oxide synthesis or transduction of nitric oxide signals through soluble guanylate cyclase. We anticipate that our anatomical studies will show, at the electron micrsocopic level, that ionotropic glutamate receptors are frequently associated with nNOS and soluble guanylate cyclase immunoreactivity. Metabotropic receptors may be similarly associated, but at the electron microscopic level we expect to find that the latter receptors lie presynaptically with respect to nNOS neurons while the former predominantly occur postsynaptically, i.e. on nNOS immunoreactive dendrites or neurons in NTS.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059593-06
Application #
6767677
Study Section
Cardiovascular and Renal Study Section (CVB)
Program Officer
Velletri, Paul A
Project Start
1998-12-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
6
Fiscal Year
2004
Total Cost
$220,500
Indirect Cost
Name
University of Iowa
Department
Neurology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Lin, Li-Hsien; Jin, Jingwen; Nashelsky, Marcus B et al. (2014) Acid-sensing ion channel 1 and nitric oxide synthase are in adjacent layers in the wall of rat and human cerebral arteries. J Chem Neuroanat 61-62:161-8
Talman, William T; Lin, Li-Hsien (2013) Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii. Auton Neurosci 175:9-16
Talman, William T (2012) Views of translational research from a somewhat translational scientist. J Investig Med 60:863-8
Lin, Li-Hsien; Nitschke Dragon, Deidre; Jin, Jingwen et al. (2012) Decreased expression of neuronal nitric oxide synthase in the nucleus tractus solitarii inhibits sympathetically mediated baroreflex responses in rat. J Physiol 590:3545-59
Lin, Li-Hsien; Dragon, Deidre Nitschke; Jin, Jingwen et al. (2011) Targeting neurons of rat nucleus tractus solitarii with the gene transfer vector adeno-associated virus type 2 to up-regulate neuronal nitric oxide synthase. Cell Mol Neurobiol 31:847-59
Lin, L H; Langasek, J E; Talman, L S et al. (2010) Feline immunodeficiency virus as a gene transfer vector in the rat nucleus tractus solitarii. Cell Mol Neurobiol 30:339-46
Taktakishvili, Otar M; Lin, Li-Hsien; Vanderheyden, Andrew D et al. (2010) Nitroxidergic innervation of human cerebral arteries. Auton Neurosci 156:152-3
Lin, Li-Hsien (2009) Glutamatergic neurons say NO in the nucleus tractus solitarii. J Chem Neuroanat 38:154-65
Boysen, Nicholas C; Dragon, Deidre Nitschke; Talman, William T (2009) Parasympathetic tonic dilatory influences on cerebral vessels. Auton Neurosci 147:101-4
Nayate, Ameya; Moore, Steven A; Weiss, Robert et al. (2009) Cardiac damage after lesions of the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 296:R272-9

Showing the most recent 10 out of 33 publications