Highly enhanced permeability of blood-brain barrier induced by repeated administration of endothelin-1 in dogs and rats.
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.
Narushima
Itaru
I
Department of Pharmacology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
Kita
Taizo
T
Kubo
Kaoru
K
Yonetani
Yukio
Y
Momochi
Chikako
C
Yoshikawa
Ichigo
I
Ohno
Norikazu
N
Nakashima
Toshikatsu
T
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
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D005456:Fluorescent Dyes; D044022:Receptor, Endothelin A; D019793:Fluorescein