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

在内毒素血症动物模型中，心输出量的分布受到干扰，在一些区域中具有相对的过度灌注，而在其他区域中具有低灌注。内皮源性舒张因子（EDRF/NO）的释放改变已被认为是脂多糖（LPS）引起的血管舒张反应异常的最终共同途径。一氧化氮在内皮依赖性舒张中起主要作用。此外，内皮源性超极化因子（EDHF），一种与一氧化氮不同的未鉴定的可扩散物质，通过打开底层血管平滑肌中的K+通道而有助于内皮依赖性舒张。本研究旨在阐明EDRF（NO和EDHF）在感染性休克血管舒张中的作用。用腹膜内注射LPS（50 mg/kg）处理雄性Sprague-Dawley大鼠<-1>，并通过测量内毒素的血清浓度证实LPS处理的大鼠中的败血症。在动物的动脉树中测量等长张力、平滑肌细胞的膜电位以及组织中的环GMP（使用酶免疫测定法）和iNOS蛋白（使用Western印迹分析法）水平。LPS组大鼠肠系膜动脉cGMP水平显著高于主动脉、颈动脉和肾动脉。在L-精氨酸的存在下，在主动脉和肠系膜动脉，但不是颈动脉或肾动脉，环GMP浓度增加。LPS处理的大鼠血管中诱导iNOS蛋白的表达。而iNOS蛋白的表达水平在不同血管间无明显差异。这些结果表明，动脉树之间的环GMP水平的异质性和组织环GMP和iNOS蛋白水平的大鼠血管与内毒素血症之间的差异。

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.