Effect of Ebselen on Contractile Responses in Perfused Rabbit Basilar Artery
作者:
Takashi Takase,
Tomio Ohta,
Ryusuke Ogawa,
Masao Tsuji,
Yoji Tamura,
Shuji Kazuki,
Takashi Miyamoto,
期刊:
Neurosurgery
(OVID Available online 1999)
卷期:
Volume 44,
issue 2
页码: 370-377
ISSN:0148-396X
年代: 1999
出版商: OVID
关键词: Ebselen;Endothelins;Oxyhemoglobins;Protein kinase C;Rabbits
数据来源: OVID
摘要:
OBJECTIVE:To evaluate the possible role of the antioxidant ebselen in the treatment of cerebral vasospasm, we examined the effects of ebselen on the vasoactive mechanisms induced by endothelin (ET)-1, oxyhemoglobin, and oxygen-derived radicals.METHODS:Isolated rabbit basilar arteries with intact endothelium were fixed in a perfusion system and perfused intraluminally. Contraction of the artery was detected as an increase in perfusion pressure.RESULTS:Ebselen, in a certain concentration range (3 × 10-6and 10-5mol/L), significantly reduced the contractile response to ET-1 (10-10to 10-8mol/L) but not the contraction induced by 40 mmol/L potassium. It reduced the contraction induced by 10-4mol/L 1,2-dioctanoyl-sn-glycerol, a protein kinase C activator. Addition of 10-5mol/L dithiothreitol, a sulfhydryl-reducing agent, partially reversed the inhibitory effects of ebselen on ET-1- and 1,2-dioctanoyl-sn-glycerol-induced contractions. Ebselen (10-5mol/L) as well as a combination of catabase (1000 units/mL) and superoxide dismutase (150 units/mL) inhibited the potentiating effects of oxyhemoglobin (10-5mol/L) on ET-1-induced contraction. Both ebselen and catalase inhibited the contractile response to hydroxyl radical generated by ferrous ion (10-3mol/L) plus hydrogen peroxide (10-2mol/L). Ebselen reduced the response to potassium when a high dose (3 × 10-5mol/L) was applied and failed to preserve contractility of the preparation after exposure to hydroxyl radical.CONCLUSION:Ebselen suppressed ET-1-induced contraction and synergetic interaction between oxyhemoglobin and ET-1, where free radical formation was involved. These effects may result from modification of the intracellular regulatory system including protein kinase C, as well as from protection against free radicals.
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