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Role of endothelium-derived relaxing factors (EDRFs) in vasodilation during septic shock.

内皮源性舒张因子（EDRF）在感染性休克期间血管舒张中的作用。

基本信息

批准号：
09671573
负责人：
NAKASHIMA Mikio
金额：
$ 1.98万
依托单位：
SAGA MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

项目摘要

In endotoxemic animal models, the distribution of cardiac output is disturbed, with relative hyperperfusion in some regions and hypoperfusion in others. Altered release of endothelium-derived relaxing factors (EDRF/NO) has been proposed as a final common pathway underlying the abnormal vasodilator responses to lipopolysaccharide (LPS). Nitric oxide plays a major role in endothelium-dependent relaxations. In addition, endothelium-derived hyperpolarizing factor (EDHF), an unidentified diffusible substance distinct from nitric oxide contributes to endothelium-dependent relaxations by opening K+ channels in the underlying vascular smooth muscle. The present study was designed to elucidate the in vitro role of EDRFs (NO and EDHF) in vasodilation during septic shock. Male Sprague-Dawley rats were treated with either an intraperitoneal injection of LPS (50 mg kg^<-1>), and septicemia in LPS-treated rats was confirmed by measuring serum concentration of endotoxin. The isometric tension, the membrane potential of smooth muscle cells, and tissue levels of cyclic GMP (using enzyme immunoassay) and iNOS protein (using Western blot analysis) were measured in the arterial tree of the animals. In the LPS-treated rat, the level of cyclic GMP was significantly grater in mesenteric artery than those in aorta, carotid and renal arteries. In the presence of L-arginine, the cyclic GMP concentration in the aorta and mesenteric arteries, but not the carotid or renal arteries, was increased. Expression of iNOS protein was induced in the blood vessels of LPS-treated rats. However, the expression levels of iNOS protein were not singificantly different among those blood vessels. These results indicate that a heterogeneity of cyclic GMP levels among arterial trees and a discrepancy between tissue cyclic GMP and iNOS protein levels of the rat blood vessels with endotoxemia.

在内毒素血症动物模型中，心输出量的分布受到干扰，部分区域相对高灌注区，另一些区域低灌注区。内皮源性松弛因子(EDRF/NO)的改变释放被认为是脂多糖(LPS)引起的血管扩张反应异常的最终共同途径。一氧化氮在内皮依赖性松弛中起主要作用。此外，内皮衍生超极化因子(EDHF)是一种不同于一氧化氮的未知扩散性物质，它通过开放基础血管平滑肌上的K+通道来促进内皮依赖的松弛。本研究旨在阐明EDRFs(NO和EDHF)在感染性休克血管扩张中的体外作用。给雄性SD大鼠腹腔注射脂多糖(50 mg·kg~(-1))，通过测定血清内毒素浓度来确定败血症的发生。测定动脉树等长张力、平滑肌细胞膜电位、组织环化GMP(酶免疫法)和诱导型一氧化氮合酶(INOS)水平。在内毒素处理的大鼠，肠系膜动脉的环GMP水平明显高于主动脉、颈动脉和肾动脉。在L-精氨酸存在下，主动脉和肠系膜动脉的cGMP浓度增加，而颈动脉和肾动脉则无明显变化。诱导型一氧化氮合酶蛋白在内毒素处理的大鼠血管中表达。而iNOS蛋白在不同血管中的表达水平无明显差异。提示内毒素血症大鼠动脉血管环GMP水平存在异质性，组织环GMP和iNOS蛋白水平存在差异。