Effects of the angiotensin II antagonist 1-sar-8-ala-angiotensin II in hypertension in man

Abstract

The angiotensin II antagonist 1-sar-8-ala-angiotensin II (saralasin) was infused in 46 patients with hypertension of various etiology (essential, renal arterial or parenchymal disease, primary hyperaldosteronism), before and/or during Na volume depletion obtained by chlorthalidone and low Na diet. When saralasin was infused in 25 patients ingesting 130 mmol of Na/day, including patients with proven renovascular hypertension, the changes in mean arterial pressure ranged from +10 to -7 mmHg (mean: +0.20 mmHg) and were not related to the plasma renin concentration (PRC) (r = -0.11). During Na volume depletion, saralasin induced changes in mean arterial pressure, ranging from +21 to -76 mmHg, which were closely related to log PRC (n = 32; r = -0.87). Combined Na depletion and antagonism of agiotensin II normalized mean arterial pressure (.ltoreq. 100 mmHg) in 21 of the 32 patients, while pressure remained between 106 and 147 mmHg in 11 poor responders, so that pressor mechanisms other than Na volume and angiotensin must be responsible for the remaining elevation of pressure in these patients. Arterial pressure is not dependent on the immediate pressor effects of angiotensin II in Na replete patients and in Na deplete subjects whose PRC remains low, while it is at least partly angiotensin II dependent during Na volume depletion in the others. The results cast doubts on the clinical usefulness of saralasin in the investigation of patients with hypertension, under these conditions.