Rolo of NO as a causative factor for hypertensive cerebral injury

为了阐明NO在高血压脑损伤中的作用，我们研究了卒中易发SHR （SHRSP）大脑皮层的病理生理变化。(1)重度高血压患者SI-IRSP脑皮质出现水肿改变和/或脑软化。(2)免疫组化检查显示，SHRSP脑组织内皮细胞黏附分子ICAM-1表达升高，血脑屏障构成蛋白GLUT-1表达降低。(3)白细胞粘附分子Mac-1在SHRSP中的表达明显高于WKY。(4) SHRSP组血浆NO代谢物含量较高。(5)在SHRSP白细胞中，RT-PCR中iNOS的表达也较高。(6)脂多糖（激活白细胞）增强了SHRSP的这些病理生理变化，但s -甲基异硫脲（iNOS抑制剂）对其有保护作用。提示一氧化氮通过增强白细胞-内皮细胞黏附作用在高血压脑损伤中的重要作用。

To elucidatc the role of NO as a causative factor for hypertensive cerebral injury, pathophysiological changes were investigated in stroke-prone SHR (SHRSP) cerebral cortex.(1)Edematosu changes and/or cerebral softening were found ini SI-IRSP cerebral cortex suffering from severe hypertension.(2)Immunohistochemical examination revealed increased expression of ICAM-1 (adhesion molecule of endothelial cells) and decreased expression of GLUT-1 (constitutive protein of blood=brain barrier) in such SHRSP brain.(3)Mac-1 (adhesion molecule in leukocytes) expression was much higher in SHRSP than in WKY.(4)Plasma NO metabolites content was higher in SHRSP.(5)iNOS expression in RT-PCR was also higher in SHRSP leukocytes.(6)These pathophysiological changes in SHRSP were enhanced by lipopolysaccharide (activation of leukocytes), but protected by S-mthylisothiourea (iNOS inhibitor).These results indicate the important role of NO generated by enhansed leukocyte-endothelial cell adhesion in hypertensive cerebral injury.