Intrathecal administration of endothelin-1 receptor antagonist ameliorates autoimmune encephalomyelitis in Lewis rats

Neuroreport. 2001 May 25;12(7):1465-8. doi: 10.1097/00001756-200105250-00034.

Abstract

The role of endothelin-1 (ET-1) in the development of experimental autoimmune encephalomyelitis (EAE) was studied by the blocking the action of ET-1 with a receptor antagonist, BQ-123. Intrathecal administration of BQ-123 significantly ameliorated EAE progression at the peak stage of EAE (p<0.05). By immunohistochemistry, ED-1-positive macrophages in EAE lesions were identified as major producers of ET-1, whereas the immunoreactivity of ET-1 on brain cells, such as astrocytes, was dramatically increased in accordance with the progression of EAE. This study points to a putative pro-1nflammatory role for ET-1 in the pathogenesis of EAE. One possible application for the ET-1 receptor antagonist might be helpful in the therapy of autoimmune neurological disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Blood Vessels / drug effects
  • Blood Vessels / pathology
  • Blood Vessels / physiopathology
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / pathology
  • Demyelinating Diseases / physiopathology*
  • Disease Models, Animal
  • Encephalitis / drug therapy
  • Encephalitis / pathology
  • Encephalitis / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Endothelin Receptor Antagonists*
  • Endothelin-1 / antagonists & inhibitors*
  • Endothelin-1 / metabolism
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry
  • Injections, Spinal
  • Male
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Endothelin / metabolism
  • Spinal Cord / drug effects*
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Glial Fibrillary Acidic Protein
  • Peptides, Cyclic
  • Receptors, Endothelin
  • cyclo(Trp-Asp-Pro-Val-Leu)