HYPERTENSIVE AND RENAL EFFECTS OF CHRONIC LOW-LEVEL INTRA-RENAL ANGIOTENSIN INFUSION IN THE DOG

To determine whether the intrarenal sodium-retaining effects of angiotensin II (A II) can produce chronic hypertension, we infused A II at a rate (1 ng/kg per min) that did not cause a measurable immediate rise in mean arterial pressure (MAP) for 10 days directly into the renal artery of five dogs with unilateral nephrectomy. Four additional control dogs with unilateral nephrectomy were infused intravenously with A II for 10 days at 0.5 ng/kg per min. This itravenous infusion rate of A II was calculated to produce an increase in peripheral blood levels of A II at least as great as those achieved with the intrarenal infusion of A II. MAP was recorded continuously, 24 hours/day, and daily values for MAP based on approximately 720 sample points per day were determined by computerized data analysis. Intrarenal A II infusion produced an immediate fall in glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and urinary sodium (U(Na)V) and potassium (U(K)V) excretion. MAP was unchanged during the first day of the infusion period. Both GFR and ERPF remained depressed for at least 6 days of the infusion. However, sodium balance was achieved on day 2 when MAP had increased by 9 mm Hg. Subsequently, MAP continued to increase, reaching + 15 mm Hg at the end of 10 days. In contrast, there was no sodium retention or hypertension during the first 48 hours of intravenous A II infusion; yet, during days 3-10, MAP did rise by 7 mm Hg. After the intrarenal infusion of A II was stopped on day 10, there were immediate increases in GFR, ERPF, U(K)V, and especially U(Na)V, and MAP returned to control levels after a few hours. The data indicate that the intrarenal effects of A II can produce chronic sodium retention and a sustained elevation in MAP and also prevent pressure natriuresis during the hypertension.