Molecular mechanism of hypertension on pregnant transgenic mice.

(1)筑波高血压小鼠作为人类恶性高血压模型的研究筑波高血压小鼠（THM;一种携带人肾素和血管紧张素原基因的转基因小鼠）的产生是为了进一步研究各种病理条件下的肾素-血管紧张素系统。我们通过形态计量学、免疫组织化学和超微结构方法评价了这些小鼠和对照组中肾脏病变的发展。THM小鼠的血压明显高于对照组小鼠;出生后1年，血压高出约40 mmHg。THM组的肾体重比也高于对照组。形态计量学分析显示THM组肾小球硬化指数显著升高，18个月时肾小球硬化率为10%。肾血管病变程度和纤维支气管样动脉炎的发生率与肾小球硬化指数的变化趋势一致。光镜和电镜检查显示THM患者的肾有明显的纤维素样动脉炎，也有“洋葱皮样”，这两种病变都是恶性肾硬化的特征性表现。THM可能是一种很好的恶性高血压动物模型。(2)高血压转基因小鼠血管重构我们对高血压转基因小鼠（THM）高血压引起的血管损伤和血管重构进行了生理学和组织病理学分析。青春期（8周龄）THM由于增强的肾素血管紧张素系统（RAS）已经具有与成人THM中的血压相似的高血压。他们进行性发展显着的血管肥大的血管平滑肌细胞（VSMCs）的去分化和细胞外基质的积累在胸主动脉，和VSHC增生是占主导地位的腹主动脉。因此，THM是研究增强的RAS介导的血管重塑的有用的动物模型。

(1) The Tsukuba hypertensive mouse as a model of human malignant hypertensionThe renin-angiotensin, system has a pivotal role in hypertension. The Tsukuba hypertensive mouse (THM; a transgenic mouse carrying human genes for both renin and angiotensinogen) was generated to allow further examination of the renin-angiotensin system in a variety of pathologic conditions. We evaluated the development of renal lesions in these mice and in controls by morphometric, immunohistochemical and ultra-structural methods. Blood pressure was significantly higher in THM than in control mice; 1 year after birth, it was approximately 40 mmHg higher. The kidney-to-body weight ratio was also higher in THM than in control. Morphometrical analysis revealed that the glomerular sclerosis index was significantly elevated in THM with 10% of the glomeruli sclerotic at 18 months. The grade of vascular lesion and the frequency of fibronoid arteritis of the kidney exhibited the same tendency as the glomerular sclerosis index. Light and electron microscopy revealed significant fibrinoid arteritis of the kidney in THM and also "onion skinning" , both pathognomonic for malignant nephrosclerosis. THM may be an excellent model of human malignant hypertension.(2) Vascular remodeling in hypertensive transgenic miceWe physiologically and histopathologically analyzed vascular damage due to hyper' tension and vascular remodeling in hypertensive transgenic mice (THM). Pubertal(8-week -old) THM already had hypertension similar to blood pressure in adult THM due to an enhanced renin angiotensin system (RAS). They progressively developed remarkable vascular hypertrophy composed of dedifferentiation of vascular smooth muscle cells (VSMCs) and extracellular matrix accumulation in the thoracic aorta, and VSHC hyperplasia was predominant in the abdominal aorta. THM are therefore a useful animal model for studying vascular remodeling mediated by enhanced RAS.