Antihypertensive Effect of Prolonged Blockade of Angiotensin Formation in Benign and Malignant, one- and two-Kidney Goldblatt Hypertensive Rats

Abstract

1. The effect of chronic inhibition of angiotensin II formation was investigated in four groups of hypertensive rats. Benign hypertension was produced by placing a 0·25 mm-diameter silver clip on the renal artery; a 0·20 mm clip was used to create malignant hypertension. A two-kidney model had a clip plus intact contralateral kidney and a one-kidney model had a clip plus contralateral nephrectomy. Benign and malignant groups were prepared in both the one-kidney and two-kidney variations. Converting enzyme inhibitor (SQ 14.225) was given to these four groups for 1 week in drinking water and average intake ranged from 33 to 77 mg/day. 2. The two malignant groups had the highest plasma renin activities and they showed a precipitous fall in arterial pressure in the first 24 h of inhibition of angiotensin formation. All groups showed an additional slow decline in pressure during the remaining 6 days of inhibition. Changes in heart rate and sodium excretion were variable but, in general, heart rate decreased during inhibition. 3. Arterial pressure did not become normal with inhibition in either of the one-kidney models: decreases to 126 and 132 mmHg were observed in the benign and malignant groups respectively. Three of the malignant one-kidney animals became uraemic with inhibition and one died before inhibition was discontinued. 4. Arterial pressure was reduced to normal pressure (95 mmHg) after 1 week of inhibition in both the benign and malignant two-kidney models. 5. It appears that normal pressure was restored in the two-kidney model but not in the one-kidney model because of the presence of the intact contralateral kidney. The physiological basis for this difference is not known but changes in renal excretory function may be involved.