Chatelain R E, DiBello P M, Ferrario C M
Br J Exp Pathol. 1980 Aug;61(4):401-10.
Aortic ligation between the renal arteries in Sprague-Dawley rats weighing 150-200 g resulted in the prompt development of either the malignant (MHY) or benign (BHY) forms of hypertension. Evolution of hypertension and vascular disease was studied in groups of MHY and BHY animals killed at 12,21 and 30 days after ligation. At 12 days MHY and BHY animals showed equally elevated mean arterial pressure (MHY: 184±6; BHY: 189±2 mmHg). MHY animals, however, were characterized by markedly increased plasma renin activity (PRA:MHY: 565±129; BHY: 85±13; sham-operated (SHAM-OP): 15±2 ng angiotensin I (AI)/ml/h) and widespread necrotizing arteritis with massive fibrinoid deposition. At 21 days fibrinoid deposits had extended to the non-ischaemic kidney, where the initiation of intimal proliferation in interlobular arteries was also present. Elevated PRA in 30-day MHY animals (MHY: 152±20; BHY: 25±2; SHAM-OP: 19±2 ng/AI/ml/h) was accompanied by generalized necrotizing arteritis, malignant nephrosclerosis and elevated blood urea nitrogen (BUN:MHY: 50±7 mg/dl; BHY: 29±1 mg/dl; P<0.025). In benign hypertensives, despite similarly elevated blood pressure necrotizing lesions were not observed. Although no MHY survived beyond 41 days of hypertension, 108 BHY were alive 60 days after aortic ligation. BHY animals studied at this time were characterized by increased blood pressure (BHY: 177±6; SHAMOP: 112±2 mmHg), normal body wt (BHY: 344±5; SHAM-OP: 353±8 g), normal PRA (BHY: 8±1; SHAM-OP: 9±1 ng AI/ml/h), normal levels of BUN (BHY: 18±2; SHAM-OP: 20±2 mg/dl) and the absence of necrotizing vascular disease in the kidney or other organs. These experiments indicate that aortic ligation in animals of this size results in the development of MHY in a significant proportion of the population (36%). This system permits the study of animals which sustain a close replica to the malignant or benign form of the human disease. Furthermore, the pathogenic mechanisms operating in one form of hypertension may be compared to those occurring in animals following the opposite course of the disease.
对体重150 - 200克的Sprague-Dawley大鼠在肾动脉之间进行主动脉结扎，会迅速引发恶性（MHY）或良性（BHY）高血压。在结扎后12、21和30天处死的MHY和BHY动物组中，研究了高血压和血管疾病的进展情况。在12天时，MHY和BHY动物的平均动脉压同样升高（MHY：184±6；BHY：189±2 mmHg）。然而，MHY动物的特征是血浆肾素活性显著增加（血浆肾素活性：MHY：565±129；BHY：85±13；假手术（SHAM-OP）：15±2 ng血管紧张素I（AI）/毫升/小时），以及广泛的坏死性动脉炎并伴有大量纤维蛋白样沉积。在21天时，纤维蛋白样沉积物已扩展至非缺血性肾脏，在那里小叶间动脉内膜增殖也已开始。30天的MHY动物血浆肾素活性升高（MHY：152±20；BHY：25±2；SHAM-OP：19±2 ng/AI/毫升/小时），同时伴有全身性坏死性动脉炎、恶性肾硬化和血尿素氮升高（血尿素氮：MHY：50±7毫克/分升；BHY：29±1毫克/分升；P<0.025）。在良性高血压动物中，尽管血压同样升高，但未观察到坏死性病变。尽管没有MHY动物在高血压41天后存活，但108只BHY动物在主动脉结扎后60天仍然存活。此时研究的BHY动物的特征为血压升高（BHY：177±6；SHAMOP：112±2 mmHg）、体重正常（BHY：344±5；SHAM-OP：353±8克）、血浆肾素活性正常（BHY：8±1；SHAM-OP：9±1 ng AI/毫升/小时）、血尿素氮水平正常（BHY：18±2；SHAM-OP：20±2毫克/分升），且肾脏或其他器官无坏死性血管疾病。这些实验表明，对这种大小的动物进行主动脉结扎会使相当比例的群体（36%）发生MHY。该系统允许对与人类疾病的恶性或良性形式极为相似的动物进行研究。此外，一种高血压形式中的致病机制可与疾病发展为相反过程的动物中的致病机制进行比较。
