Possible role of endothelin in the pathogenesis of cerebral vasospasm

T. Shigeno, T. Mima, Masashi Yanagisawa, A. Saito, A. Fujimori, R. Shiba, K. Goto, S. Kimura, K. Yamashita, Y. Yamasaki, T. Masaki, K. Takakura

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21 Scopus citations

Abstract

Since the discovery of endothelin-1 (ET-1), its involvement in cerebral vasospasm after subarachnoid hemorrhage (SAH) has been suspected. We performed various experiments, first to demonstrate the presence of ET in both patients and dogs with SAH, and second to examine the effects of ET synthesis inhibition in experimental vasospasm. Here we report that ET was present in both plasma and cerebrospinal fluid (CSF) in SAH, but did not correlate with vasospasm. However, ET was locally expressed in the vascular endothelium in vasospasm. Several therapeutic approaches causing the inhibition of ET synthesis were effective in preventing the development of vasospasm. Such approaches utilized drugs that inhibited RNA and DNA synthesis. Among them, actinomycin D treatment was most effective. We also utilized phosphoramidon, a recently found conversion inhibitor of big ET to ET. However, this product failed to ameliorate the development of vasospasm. Therefore, although we cannot yet conclude that ET is the main cause of cerebral vasospasm, it may, at least, act as one of the modifying factors in cerebral vasospasm.

Original languageEnglish (US)
Pages (from-to)S480-S483
JournalJournal of Cardiovascular Pharmacology
Volume17
StatePublished - Jan 1 1991

Keywords

  • Actinomycin D
  • Cerebral vasospasm-Endothelin
  • Phosphoramidon
  • RNA synthesis

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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    Shigeno, T., Mima, T., Yanagisawa, M., Saito, A., Fujimori, A., Shiba, R., Goto, K., Kimura, S., Yamashita, K., Yamasaki, Y., Masaki, T., & Takakura, K. (1991). Possible role of endothelin in the pathogenesis of cerebral vasospasm. Journal of Cardiovascular Pharmacology, 17, S480-S483.