Angiotensin II type 1 receptors may not influence response of spinal autonomic neurons to axonal damage

Hui Tang, Jaroslav Pavel, Juan M. Saavedra, Stephen Brimijoin

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Objectives: 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 AT1 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 [125l]-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, AT 1 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. Discussion: 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.

Original languageEnglish (US)
Pages (from-to)751-760
Number of pages10
JournalNeurological research
Volume30
Issue number7
DOIs
StatePublished - Sep 2008

Keywords

  • Candesartan
  • Immunohistochemistry
  • Neurodegeneration
  • Primary sensory neurons
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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