Continuous angiotensin II blockade throughout the acute phase of one-kidney hypertension in the dog.

The importance of the renin-angiotensin system in the development and maintenance of one-kidney renal hypertension in the dog was assessed by chronically inhibiting angiotensin by continuous infusion of [Sar'-,Ala]angiotensin II or a converting enzyme inhibitor (SQ 20881). Angiotensin blockade was begun 1-2 days before renal artery constriction and continued for 6-7 days throughout the high rerun phase of hypertension. Chronic hypertension was produced despite continuous angiotensin inhibition with [Sar',Ala]angiotensin II or SQ 20881. Mean arterial pressure rose to hypertensive levels during the |Sar,Ala"]angiotensin II infusion, but the increase occurred more slowly than when the renin-angiotensin system was intact. Although chronic infusion of the angiotensin II analogue itself produced no measurable vasopressor agonism, the analogue appeared to be mildy agonistic for the kidney and adrenal cortex. Chronic SQ 20881 infusion consistently lowered mean arterial pressure by about 10 mm Hg in unilaterally nephrectomized normotensive dogs and potentiated the vasodepressor action of bradykinin. Renal artery constriction during the SQ 20881 infusion for 6 days produced a gradual increase in mean arterial pressure (18 mm Hg above the control level); discontinuation of SQ 20881 was followed by a further elevation in arterial pressure. The present observations demonstrate that chronic hypertension developed and was sustained in spite of minimal or no activation of the renin-angiotensin system during the acute high renin phase of one-kidney hypertension.