title: Highly enhanced permeability of blood-brain barrier induced by repeated administration of endothelin-1 in dogs and rats.
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.
authors.affiliation: Department of Pharmacology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Narushima
authors.forename: Taizo
authors.initials: T
authors.lastname: Kita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubo
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yonetani
authors.forename: Chikako
authors.initials: C
authors.lastname: Momochi
authors.forename: Ichigo
authors.initials: I
authors.lastname: Yoshikawa
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohno
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D019793:Fluorescein; D005456:Fluorescent Dyes; D007275:Injections, Intravenous; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D013045:Species Specificity; D013268:Stimulation, Chemical
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D005456:Fluorescent Dyes; D044022:Receptor, Endothelin A; D019793:Fluorescein