Highly enhanced permeability of blood-brain barrier induced by repeated administration of endothelin-1 in dogs and rats.
Pharmacol Toxicol
; 92(1): 21-6, 2003 Jan.
Article
in En
| MEDLINE
| ID: mdl-12710593
ABSTRACT
The effects of intracisternal administration of endothelin-1 on blood-brain barrier permeability were examined in dogs and rats. Single doses of endothelin-1 elevated blood-brain barrier permeability about two times compared with control groups in both species. However, repeated dosing with endothelin-1 at a 24 hr intervals caused a highly enhanced disruption of blood-brain barrier permeability in dogs, but not in rats, whereas the repeated administration with a 48 hr interval markedly increased the blood-brain barrier permeability in both species of animals (dogs 923%, rats more than 661%). Moreover, this abnormally enhanced permeability of blood-brain barrier in dogs was completely blocked by pretreatment with the endothelin ET-A receptor selective antagonist, S-0139, administered prior to either the first or second dosing with endothelin-1. From these results, we conclude that a repeated attack of endothelin-1 from the adventitial site of brain blood vessels produces a severe disruption of blood-brain barrier permeability through an endothelin ET-A receptor-mediated process.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Blood-Brain Barrier
/
Endothelin-1
Limits:
Animals
Language:
En
Journal:
Pharmacol Toxicol
Journal subject:
FARMACOLOGIA
/
TOXICOLOGIA
Year:
2003
Document type:
Article
Affiliation country:
Japón