THE ROLE OF ENDOTHELIUM-DERIVED CONSTRICTING FACTOR(ENDOTHELIN) IN THE PATHOGENESIS OF CEREBRAL VASOSPASM
Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||UNIVERSITY OF TOKYO |
SASAKI Tomio UNIVERSITY OF TOKYO, NEUROSURGERY ASSISTANT PROFESSOR, 医学部(病), 講師 (10134561)
IDE Katsuhisa UNIVERSITY OF TOKYO, NEUROSURGERY DOCTOR ASSISTANT, 医学部(病), 助手 (90232420)
ITO Shouichi UNIVERSITY OF TOKYO, NEUROSURGERY DOCTOR ASSISTANT, 医学部(病), 助手 (50223152)
MORIMOTO Tadashi UNIVERSITY OF TOKYO, NEUROSURGERY DOCTOR ASSISTANT, 医学部(病), 助手 (20230154)
NAKAGOMI Tadayoshi UNIVERSITY OF TOKYO, NEUROSURGERY DOCTOR ASSISTANT, 医学部(病), 助手 (90198052)
栗原 裕基 東京大学, 医学部・附属病院・第三内科, 医員
山川 健太 東京大学, 医学部・附属病院・脳神経外科, 助手 (40200589)
椿 真一 東京大学, 医学部・附属病院・脳神経外科, 助手 (40207436)
斉藤 勇 東京大学, 医学部・附属病院・脳神経外科, 助教授 (20186927)
吉本 智信 東京大学, 医学部(病)脳神経外科, 助手 (30201065)
|Project Period (FY)
1989 – 1991
Completed (Fiscal Year 1991)
|Budget Amount *help
¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1989: ¥2,600,000 (Direct Cost: ¥2,600,000)
|Keywords||SUBARACHNOID HEMORRHAGE / CEREBRAL ANEURYSM / CEREBRAL VASOSPASM / ENDOTHELIN / ENDOTHELIAL CELLS / ENDOTHELIUM-DERIVED CONSTRICTING FACTOR / CEREBRAL BLOOD FLOW / クモ膜下出血 / 血管内皮細胞|
(1)Endothelin(ET-1) at concentrations of 10^<-12>-3XlO^<-8>M elicited dose-dependent contractions of canine, rabbit and monkey basilar arteries in vitro. The maximum tension was larger than that induced by 4OmM KCl.
(2)ET-1-induced contarction was activated in the canine basilar artery exposed to subarachnoid hemorrhage(SAH).
(3)An intracisternal injection of 6-1.2X10^<-12>mol/kg of ET-1 caused biphasic contraction of the canine basilar artery lasting for more than 24 hours. The initial phase of the contraction accompanied remarkable changes in vital signs such as an acute rise of blood pressure, bradycardia and respiratory arrest.
(4)ET-1 was injected into the cisterna magna of cats and rCBF was measured by the hydrogen clearance method before and every 30 minutes for 180 minutes after the injection. ET-1(10^<-11>moland 10^<-9>mol) induced a significant decrease in rCBF. The effects of ET-1 on rCBF were mediated, at least in part, by Ca^<2+>, because pretreatment with intracisternally injected nicardipine prevented the changes.
(5)Plasma levels of ET-1 were measured in SAH patients, Concentrations of plasma ET-1 in SAH patients with va sospasm were a little higher than those in SAH patients without vasospasm.
(6)The effects of a specific antagonist for ET-1 receptor(BQ-485) on the occurrence of vasospasm were examined in the canine SAH models. Pretreatment of SAH dogs with BQ-485 decreased the degree of angiographic vasospasm by about 15% on Day 7.
These results indicate that ET-1 produced in cerebrovascular endothelium contpibute to the occurrence of vasospasm at least in part, although it is not a main causative factor.
Report (4 results)
Research Products (23 results)