Highly enhanced permeability of blood-brain barrier induced by repeated administration of endothelin-1 in dogs and rats |
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Authors: | Narushima Itaru Kita Taizo Kubo Kaoru Yonetani Yukio Momochi Chikako Yoshikawa Ichigo Ohno Norikazu Nakashima Toshikatsu |
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Institution: | Department of Pharmacology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. |
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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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