TY - JOUR
T1 - Possible role of endothelin in the pathogenesis of cerebral vasospasm
AU - Shigeno, T.
AU - Mima, T.
AU - Yanagisawa, Masashi
AU - Saito, A.
AU - Fujimori, A.
AU - Shiba, R.
AU - Goto, K.
AU - Kimura, S.
AU - Yamashita, K.
AU - Yamasaki, Y.
AU - Masaki, T.
AU - Takakura, K.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
KW - Actinomycin D
KW - Cerebral vasospasm-Endothelin
KW - Phosphoramidon
KW - RNA synthesis
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U2 - 10.1097/00005344-199100177-00138
DO - 10.1097/00005344-199100177-00138
M3 - Article
C2 - 1725419
AN - SCOPUS:0026349274
SN - 0160-2446
VL - 17
SP - S480-S483
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
ER -