Cerebral microvascular responses to endothelins: The role of ET(A) receptors

O. Sagher, Y. Jin, Quoc-Anh Thai, A. Fergus, N. F. Kassell, K. S. Lee

Research output: Contribution to journalArticle

Abstract

The regulatory role of endothelins in cerebral microvessels was investigated in a recently developed model system which allows the study of small cerebral vessels in their normal microenvironment. Using brain slices of the rat neocortex, it was shown that the isopeptide endothelin-3 (ET-3) had no effect on cerebral microvessels, while the isopeptide endothelin-1 (ET-1) produced a potent, dose-dependent vasoconstriction. When a recently developed antagonist of ET(A) receptors (Cyclo-[D-Asp-L-Pro-D-Val-L-Leu-D-Trp]; ETant) was administered prior to treatment with ET-1, the vasoconstrictor response to ET-l was inhibited in a dose-dependent manner. When ETant was administered after the establishment of a constriction by ET-l, the constrictor response to ET-1 was partially reversed, and this effect was weaker than that seen in the pre-treatment paradigm. These findings indicate that constrictor responses to ET-1 in cerebral microvessels are mediated by ET(A) receptors. Inasmuch as endothelins have been implicated in pathological forms of vasoconstriction in the CNS, the present findings also suggest that endothelin antagonists may be useful in the treatment of cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
JournalBrain Research
Volume658
Issue number1-2
StatePublished - 1994
Externally publishedYes

Fingerprint

Endothelins
Endothelin-1
Microvessels
Vasoconstriction
Endothelin-3
Neocortex
Vasoconstrictor Agents
Brain Ischemia
Constriction
Brain

Keywords

  • Cerebral microvessel
  • Endothelin
  • Endothelin(a) receptor
  • Endothelin-1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sagher, O., Jin, Y., Thai, Q-A., Fergus, A., Kassell, N. F., & Lee, K. S. (1994). Cerebral microvascular responses to endothelins: The role of ET(A) receptors. Brain Research, 658(1-2), 179-184.

Cerebral microvascular responses to endothelins : The role of ET(A) receptors. / Sagher, O.; Jin, Y.; Thai, Quoc-Anh; Fergus, A.; Kassell, N. F.; Lee, K. S.

In: Brain Research, Vol. 658, No. 1-2, 1994, p. 179-184.

Research output: Contribution to journalArticle

Sagher, O, Jin, Y, Thai, Q-A, Fergus, A, Kassell, NF & Lee, KS 1994, 'Cerebral microvascular responses to endothelins: The role of ET(A) receptors', Brain Research, vol. 658, no. 1-2, pp. 179-184.
Sagher O, Jin Y, Thai Q-A, Fergus A, Kassell NF, Lee KS. Cerebral microvascular responses to endothelins: The role of ET(A) receptors. Brain Research. 1994;658(1-2):179-184.
Sagher, O. ; Jin, Y. ; Thai, Quoc-Anh ; Fergus, A. ; Kassell, N. F. ; Lee, K. S. / Cerebral microvascular responses to endothelins : The role of ET(A) receptors. In: Brain Research. 1994 ; Vol. 658, No. 1-2. pp. 179-184.
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