title: Angiotensin II type 1 receptors may not influence response of spinal autonomic neurons to axonal damage.
abstract: OBJECTIVE
  Angiotensin II can promote cell stress, and the expression of its AT1 receptor is characteristic of neuronal populations that die off in multiple systems atrophy and Parkinson's disease. To explore the possible significance of these facts, we undertook to: (1) clarify the distribution of AT(1) in rat neurons; (2) use selective antagonists as a means of determining whether AT1 activation predisposes stressed neurons to die.
  
  
  METHODS
  AT1-expression was examined by immunohistochemistry and by autoradiography for [125I]-sarcosine1-angiotensin II binding in sensory, motor and autonomic neurons. To induce cell loss in a specific neuronal population, rats were given systemic i.v. injection of anti-acetylcholinesterase antibodies, which cause a delayed death of pre-ganglionic sympathetic neurons in the intermediolateral nucleus (IML). As pharmacologic intervention, some immunolesioned rats were treated with the selective AT1 antagonist, Candesartan.
  
  
  RESULTS
  Immunohistochemistry and autoradiography revealed AT1 expression in dorsal root ganglia, superior cervical ganglion. In the dorsal horn of the spinal cord, AT1 immunostainining and angiotensin binding were both prominent. In ventral horn and IML, immunoreactivity for AT1 and choline acetyltransferase co-localized in pre-ganglionic sympathetic and somatic motor neurons. Immunolesion caused over 50% loss of IML perikarya within 3 months. Concurrent treatment with the AT1 antagonist, Candesartan, did not affect the outcome.
  
  
  CONCLUSIONS
  AT1 expression is surprisingly widespread in sensory, autonomic and somatic motor neurons of the rat. This expression may be important to the normal physiology of these systems. Present data, however, do not support the concept that AT1 activation contributes to the loss of autonomic neurons after axonal damage.
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Foundation, Rochester, MN 55905, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pavel
authors.forename: Juan M
authors.initials: JM
authors.lastname: Saavedra
authors.forename: Stephen
authors.initials: S
authors.lastname: Brimijoin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000276:immunology / Q000378:metabolism; D000320:Adrenergic Fibers / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001713:Biphenyl Compounds; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009476:Neurons, Efferent / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002800:Cholinesterase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000110:Acetylcholinesterase; D000109:Acetylcholine; C081643:candesartan