Cardiovascular Response to Glutamate Nitric Oxide

Summary

Principal Investigator: WILLIAM contact TALMAN
Affiliation: University of Iowa
Country: USA
Abstract: 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.
Funding Period: 1998-12-15 - 2009-06-30
more information: NIH RePORT

Top Publications

  1. doi Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii
    William T Talman
    Department of Neurology, Carver College of Medicine University of Iowa and Veterans Affairs Healthcare System, Iowa City, IA 52242, USA
    Auton Neurosci 175:9-16. 2013
  2. doi Views of translational research from a somewhat translational scientist
    William T Talman
    Laboratory of Neurobiology, Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    J Investig Med 60:863-8. 2012
  3. pmc Decreased expression of neuronal nitric oxide synthase in the nucleus tractus solitarii inhibits sympathetically mediated baroreflex responses in rat
    Li Hsien Lin
    Laboratory of Neurobiology, Department of Neurology, Roy and Lucille Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
    J Physiol 590:3545-59. 2012
  4. pmc Targeting neurons of rat nucleus tractus solitarii with the gene transfer vector adeno-associated virus type 2 to up-regulate neuronal nitric oxide synthase
    Li Hsien Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    Cell Mol Neurobiol 31:847-59. 2011
  5. pmc Nitroxidergic innervation of human cerebral arteries
    Otar M Taktakishvili
    Department of Neurology, Univ of Iowa, Iowa City, IA 52242, USA
    Auton Neurosci 156:152-3. 2010
  6. pmc Feline immunodeficiency virus as a gene transfer vector in the rat nucleus tractus solitarii
    L H Lin
    Department of Neurology, 1191 ML, University of Iowa, Iowa City, IA 52242, USA
    Cell Mol Neurobiol 30:339-46. 2010
  7. pmc Glutamatergic neurons say NO in the nucleus tractus solitarii
    Li Hsien Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    J Chem Neuroanat 38:154-65. 2009
  8. pmc Parasympathetic tonic dilatory influences on cerebral vessels
    Nicholas C Boysen
    Laboratory of Neurobiology, University of Iowa, Iowa City, IA 52242, USA
    Auton Neurosci 147:101-4. 2009
  9. pmc Cardiac damage after lesions of the nucleus tractus solitarii
    Ameya Nayate
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    Am J Physiol Regul Integr Comp Physiol 296:R272-9. 2009
  10. pmc Colocalization of neurokinin-1, N-methyl-D-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii
    L H Lin
    Department of Neurology, University of Iowa, 1191 Medical Laboratories, Iowa City, IA 52242, USA
    Neuroscience 154:690-700. 2008

Scientific Experts

  • Li Hsien Lin
  • WILLIAM contact TALMAN
  • Otar M Taktakishvili
  • Ameya Nayate
  • Nicholas C Boysen
  • Marcus B Nashelsky
  • Andrew D Vanderheyden
  • Steven A Moore
  • Deidre Nitschke Dragon
  • Robert Weiss

Detail Information

Publications17

  1. doi Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii
    William T Talman
    Department of Neurology, Carver College of Medicine University of Iowa and Veterans Affairs Healthcare System, Iowa City, IA 52242, USA
    Auton Neurosci 175:9-16. 2013
    ..Thus, the effect of the toxins may depend on an action of SAP independent of the effects of the SAP conjugates on targeted neuronal types...
  2. doi Views of translational research from a somewhat translational scientist
    William T Talman
    Laboratory of Neurobiology, Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    J Investig Med 60:863-8. 2012
    ..Finding treatments, while always an aim of biomedical research, may arise as a result of basic studies that were not originally aimed at a target of translational research...
  3. pmc Decreased expression of neuronal nitric oxide synthase in the nucleus tractus solitarii inhibits sympathetically mediated baroreflex responses in rat
    Li Hsien Lin
    Laboratory of Neurobiology, Department of Neurology, Roy and Lucille Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
    J Physiol 590:3545-59. 2012
    ..We suggest that, at the basal state, nNOS is maximally engaged. Thus, its upregulation does not augment the baroreflex...
  4. pmc Targeting neurons of rat nucleus tractus solitarii with the gene transfer vector adeno-associated virus type 2 to up-regulate neuronal nitric oxide synthase
    Li Hsien Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    Cell Mol Neurobiol 31:847-59. 2011
    ..Therefore, we conclude that AAV2 is an effective viral vector in chronically transducing NTS neurons and that AAV2nNOS can be used as a specific gene transfer tool to study the role of nNOS in CNS neurons...
  5. pmc Nitroxidergic innervation of human cerebral arteries
    Otar M Taktakishvili
    Department of Neurology, Univ of Iowa, Iowa City, IA 52242, USA
    Auton Neurosci 156:152-3. 2010
    ....
  6. pmc Feline immunodeficiency virus as a gene transfer vector in the rat nucleus tractus solitarii
    L H Lin
    Department of Neurology, 1191 ML, University of Iowa, Iowa City, IA 52242, USA
    Cell Mol Neurobiol 30:339-46. 2010
    ..The cell-type specificity of FIV in the NTS may provide a molecular method to study local physiological functions mediated by potential neurotransmitters in the NTS...
  7. pmc Glutamatergic neurons say NO in the nucleus tractus solitarii
    Li Hsien Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    J Chem Neuroanat 38:154-65. 2009
    ..Thus, taken together, these neuroanatomical data support the hypothesis that glutamate and NO may interact with each other to regulate cardiovascular and likely other visceral functions through the NTS...
  8. pmc Parasympathetic tonic dilatory influences on cerebral vessels
    Nicholas C Boysen
    Laboratory of Neurobiology, University of Iowa, Iowa City, IA 52242, USA
    Auton Neurosci 147:101-4. 2009
    ..Ganglion removal led to reduced cerebral blood flow without changing blood pressure. Thus, parasympathetic nerves provide tonic vasodilatory input to cerebral blood vessels...
  9. pmc Cardiac damage after lesions of the nucleus tractus solitarii
    Ameya Nayate
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    Am J Physiol Regul Integr Comp Physiol 296:R272-9. 2009
    ..This study supports the hypothesis that NTS lesions interrupting the baroreflex may induce cardiac arrhythmias and myocardial changes similar to those seen in humans with central lesions and may lead to sudden cardiac death...
  10. pmc Colocalization of neurokinin-1, N-methyl-D-aspartate, and AMPA receptors on neurons of the rat nucleus tractus solitarii
    L H Lin
    Department of Neurology, University of Iowa, 1191 Medical Laboratories, Iowa City, IA 52242, USA
    Neuroscience 154:690-700. 2008
    ..The data support our hypothesis, provide an anatomical framework for glutamate and SP interactions, and may explain the loss of baroreflexes when NTS neurons, which could respond to glutamate as well as SP, are killed...
  11. pmc Identification and localization of cell types that express endothelial and neuronal nitric oxide synthase in the rat nucleus tractus solitarii
    L H Lin
    Department of Neurology, University of Iowa, VAMC 1 10W19, MS 151, Iowa City, IA 52242, USA
    Brain Res 1171:42-51. 2007
    ....
  12. pmc Neuronal nitric oxide mediates cerebral vasodilatation during acute hypertension
    William T Talman
    Laboratory of Neurobiology, Department of Neurology, VAHCS, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Brain Res 1139:126-32. 2007
    ..These findings further support the hypothesis that NO released from parasympathetic fibers contributes to cerebral vasodilatation during acute hypertension...
  13. pmc Parasympathetic stimulation elicits cerebral vasodilatation in rat
    William T Talman
    Laboratory of Neurobiology, Department of Neurology, VAMC and Carver College of Medicine, University of Iowa, Iowa City, IA 52246, USA
    Auton Neurosci 133:153-7. 2007
    ..In the current study approaching the ganglion through an incision over the zygomatic arch provided clear exposure of the ganglion and stimulation of the ganglion with that approach led to vasodilatation...
  14. ncbi NO and central cardiovascular control: a simple molecule with a complex story
    William T Talman
    Hypertension 48:552-4. 2006
  15. ncbi Vesicular glutamate transporters and neuronal nitric oxide synthase colocalize in aortic depressor afferent neurons
    L H Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    J Chem Neuroanat 32:54-64. 2006
    ..These results support our hypothesis and suggest prominent roles of VGLUT2-IR containing neurons and VGLUT3-IR containing neurons in transmitting cardiovascular signals via the ADN to the brain stem...
  16. ncbi Nitroxidergic neurons in rat nucleus tractus solitarii express vesicular glutamate transporter 3
    L H Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52242, USA
    J Chem Neuroanat 29:179-91. 2005
    ..These findings support our hypothesis that neurons and fibers containing VGLUT3 lie in close proximity to those containing nNOS and that both proteins colocalize in some neurons and fibers in the NTS...
  17. ncbi Soluble guanylate cyclase and neuronal nitric oxide synthase colocalize in rat nucleus tractus solitarii
    L H Lin
    Department of Neurology, University of Iowa, Iowa City, IA 52246, USA
    J Chem Neuroanat 29:127-36. 2005
    ..These data support our hypothesis and provide anatomical support for the suggestion that nitroxidergic activation of the NTS involves sGC...