Effects of MK-886, a leukotriene biosynthesis inhibitor, in a rabbit model of endotoxic shock

被引：13

作者：

Can, C ^{[1
]}

Çinar, MG ^{[1
]}

Ülker, S ^{[1
]}

Evinç, A ^{[1
]}

Kosay, S ^{[1
]}

机构：

[1] Ege Univ, Fac Med, Dept Pharmacol, TR-35100 Bornova, Turkey

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1998年 / 350卷 / 2-3期

关键词：

endotoxic shock; (rabbit); hypotension; leukotriene; MK-886;

D O I：

10.1016/S0014-2999(98)00262-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Leukotrienes are one of the biological mediators that play a role in endotoxic shock. In this study, we investigated the effects of a leukotriene biosynthesis inhibitor, MK-886, in a rabbit model of endotoxic shock. Lipopolysaccharide (Escherichia coli serotype 055:B5) infusion (1 mg kg(-1) h(-1)) to rabbits caused a biphasic decline in arterial blood pressure and decreased the vasoresponsiveness to phenylephrine, potassium chloride, sodium nitroprusside and acetylcholine in abdominal aortic rings. Oral administration of MK-886 (3-(1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl(-2,2-dimethylpropanoic acid) (5 mg/kg) 3 h prior to lipopolysaccharide infusion significantly inhibited the decline in arterial blood pressure and enhanced the responsiveness to phenylephrine and acetylcholine, whereas the changes in sodium nitroprusside and potassium chloride responses were not significant. However, the pD(2) (-log EC50) values for sodium nitroprusside in this group were higher than those of the group that received lipopolysaccharide alone. Neither the administration of the vehicle alone to endotoxemic rabbits, nor MK-886 administration to control animals, caused significant changes. These data suggest that MK-886 attenuates the hypotension and partially reverses the impaired vascular responsiveness observed in endotoxic shock. (C) 1998 Elsevier Science B.V. All rights reserved.

引用

页码：223 / 228

页数：6

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