Malignant Hypertension Resulting from Deoxycorticosterone Acetate and Salt Excess: ROLE OF RENIN AND SODIUM IN VASCULAR CHANGES

The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3–4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 ± 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 ± 0.02 ng/ml hour−1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 ± 0.36 ng/ml hour−1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 ± 0.01 μg/g) compared with the control level (0.132 ± 0.02 μg/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.