Experimental benign and malignant hypertension with malignant nephrosclerosis.

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.