Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 360, Issue 6, pp 639–645

Contribution of endothelin-1 to disruption of blood-brain barrier permeability in dogs

  • I. Narushima
  • T. Kita
  • K. Kubo
  • Y. Yonetani
  • C. Momochi
  • I. Yoshikawa
  • K. Shimada
  • T. Nakashima
Original Article

DOI: 10.1007/s002109900137

Cite this article as:
Narushima, I., Kita, T., Kubo, K. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1999) 360: 639. doi:10.1007/s002109900137

Abstract.

We examined the effect of intracisternal application of endothelin-1 (ET-1) on the permeability of fluorescein into the cerebrospinal fluid (CSF) in beagle dogs in order to evaluate its role in disruption of blood-brain barrier (BBB) permeability seen in the subarachnoid hemorrhage animal model. Intracisternal application of their autologous blood for producing a canine two-hemorrhage model revealed an enhanced fluorescein permeability into the CSF together with the development of cerebral vasospasm. A single dose of ET-1 (40 pmol/animal) significantly increased penetration of fluorescein compared with that in normal dogs. Although its magnitude was much less than that in the two-hemorrhage model after the first administration of ET-1, the second challenge of the same dose of ET-1 with a 48-h interval produced marked disruption of BBB permeability similar to those in the animal model. Moreover, the ET-1-induced enhancement of fluorescein permeability into the CSF was completely prevented by intracisternal pretreatment with an endothelin ETA-receptor selective antagonist, S-0139 (0.03 mg/kg), as were the ET-1-induced cerebral vasoconstriction and behavioral changes as previously reported. Thus, we conclude that ET-1 acting on the adventitial site of brain in dogs contributes to the disruption of BBB permeability via endothelin ETA-receptor mediation.

Subarachnoid hemorrhage Endothelin-1 Blood-brain barrier Endothelin ETA-receptor antagonist Two-hemorrhage model

Copyright information

© Springer-Verlag 0000

Authors and Affiliations

  • I. Narushima
    • 1
  • T. Kita
    • 1
  • K. Kubo
    • 2
  • Y. Yonetani
    • 1
  • C. Momochi
    • 3
  • I. Yoshikawa
    • 3
  • K. Shimada
    • 1
  • T. Nakashima
    • 1
  1. 1.Department of Pharmacology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan
  2. 2.Laboratory Animal Center, Nara Medical University, Kashihara, Nara 634-8521, Japan
  3. 3.Hospital Pharmacy, Nara Medical University, Kashihara, Nara 634-8521, Japan