Imaoka Masako, Sayama Ayako, Suzuki Takami, Jindo Toshimasa, Sanbuissho Atsushi
Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13, Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan.
J Toxicol Pathol. 2012 Jun;25(2):155-61. doi: 10.1293/tox.25.155.
The effect of hypertension on the occurrence of micro-hemorrhage in the pancreatic islet, known to be observed in Sprague-Dawley (SD) rats spontaneously, and endothelial markers were investigated in male Dahl-Iwai salt-sensitive (DIS, derived from SD rats), salt-resistant (DIR), and SD rats. DIS and DIR rats were fed 8% NaCl-containing diet to induce hypertension, with blood pressure measurement once a week, euthanized at 6, 8, or 12 weeks of age, and subjected to the measurement of plasma nitric oxide (NO) and von Willebrand factor (vWF) concentrations combined with histopathological examinations and immunohistochemical detections of vWF in the pancreas and kidney. As a result, hypertension was observed from 7 through 12 weeks of age in DIS rats. At 12 weeks of age, only DIS rats showed decreased plasma NO and increased vWF, indicating endothelial abnormality in the body. Histopathologically, micro-hemorrhage in the islet was observed with a similar incidence and severity in SD and DIS rats aged 12 weeks, and vWF was immunohistochemically localized in the islet endothelium with similar reactivity between age-matched SD rats. On the other hand, in the kidney, glomerular sclerosis was observed in DIS rats aged 12 weeks and accompanied broad stainability of vWF in the sclerotic glomerulus, including endothelium. In conclusion, there was no enhancement/exaggeration in the micro-hemorrhage in the pancreatic islet of hypertensive DIS rats in comparison with that in SD rats under the present experimental conditions. It is suggested that hypertension is not related to the occurrence of islet micro-hemorrhage, spontaneously observed in SD rats.
已知自发性高血压会导致斯普拉格-道利(SD)大鼠胰岛出现微出血,本研究对雄性达利-岩井盐敏感(DIS,源自SD大鼠)、盐抵抗(DIR)和SD大鼠的高血压对胰岛微出血的影响以及内皮标志物进行了研究。给DIS和DIR大鼠喂食含8%氯化钠的饮食以诱导高血压,每周测量一次血压,在6、8或12周龄时实施安乐死,并检测血浆一氧化氮(NO)和血管性血友病因子(vWF)浓度,同时对胰腺和肾脏进行组织病理学检查及vWF的免疫组化检测。结果显示,DIS大鼠在7至12周龄时出现高血压。12周龄时,只有DIS大鼠血浆NO降低且vWF升高,表明机体存在内皮异常。组织病理学上,12周龄的SD和DIS大鼠胰岛微出血的发生率和严重程度相似,且在年龄匹配的SD大鼠中,vWF免疫组化定位在胰岛内皮,反应性相似。另一方面,在肾脏中,12周龄的DIS大鼠出现肾小球硬化,硬化肾小球(包括内皮)中vWF广泛染色。总之,在本实验条件下,与SD大鼠相比,高血压DIS大鼠胰岛微出血并未增强/加重。提示高血压与SD大鼠中自发出现的胰岛微出血的发生无关。