Effect of desmethyl tirilazad, dizocilpine maleate and nimodipine on brain nitric oxide synthase activity and cyclic guanosine monophosphate during cerebral ischemia in rats

被引：9

作者：

Fernandez, MD ^{[1
]}

Meizoso, MJ ^{[1
]}

Lodeiro, MJ ^{[1
]}

Belmonte, A ^{[1
]}

机构：

[1] Univ Santiago de Compostela, Sch Med, Dept Pharmacol, E-15705 Santiago De Compostela, Spain

来源：

PHARMACOLOGY | 1998年 / 57卷 / 04期

关键词：

cerebral ischemia; nitric oxide synthase; cyclic guanosine monophosphate; desmethyl tirilazad; dizocilpine maleate; nimodipine;

D O I：

10.1159/000028239

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The present study was designed to evaluate the effects of pretreatment with a combination of desmethyl tirilazad (21-aminosteroid) plus dizocilpine maleate (N-methyl-D-aspartate receptor antagonist) and nimodipine (calcium channel antagonist) on constitutive nitric oxide synthase (cNOS) activity and cyclic guanosine monophosphate (cGMP) levels in brain homogenates of rats subjected to global cerebral transient ischemia induced by bilateral clamping of the carotids for 30 min and reduction of arterial pressure (to 50-60 mm Hg) by intravenous infusion of trimethaphan (30 mg/kg). Our results show that cerebral ischemia produced an increase in cNOS activity and cGMP levels in brain homogenates, Pretreatment with desmethyl tirilazad or dizocilpine maleate or nimodipine individually significantly suppressed (p < 0.01) the increase in cNOS activity and cGMP levels induced by cerebral ischemia, which may be related to their neuroprotective effect. Similar results were obtained with pretreatment by a combination of desmethyl tirilazad plus dizocilpine maleate plus nimodipine.

引用

页码：174 / 179

页数：6

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