Effects of an analogue of angiotensin II, [Sar1,Ile8] ATII, on blood pressure, plasma renin activity and plasma aldosterone in various forms of hypertension

Abstract

To investigate the effects of an analogue of angiotensin II (ATII), [Sar1, Ile8] ATII, on blood pressure, plasma renin activity (PRA), and plasma aldosterone (PA), the analogue was intravenously infused at a constant rate of 600 ng/kg/min for 30 minutes into 6 normal subjects and 37 untreated patients suffering from various forms of hypertension. Pressor responses with a peak at 5 to 10 minutes occurred in normal subjects and 18 essential hypertensive patients with low or normal PRA. Thirty minutes after infusion, a significant decrease in PRA with an increase in PA was observed with or without a significant increase in blood pressure in essential hypertensive patients with low or normal PRA as was also ob-served in normal subjects. On the other hand, in 8 essential hypertensive patients with high PRA, a patient with renal artery stenosis and high PRA and 3 patients with renovascular hypertension on a low sodium diet, the analogue induced a gradual decrease in blood pressure with an increase in PRA and a decrease in PA. In 2 hypertensive patients with high PRA, the analogue caused severe hypotension with bradycardia. In 4 patients with primary aldosteronism, a significant increase in blood pressure was observed without significant changes in either PRA or PA during the [Sar1, Ile8] ATII infusion.These results suggest that [Sar1, Ile8] ATII acts as a weak agonist under the normal or low secretion of renin, but as an antagonist under an excess of renin release in man, except for primary aldosteronism in which a discrepant agonistic action between vasculature and kidney or adrenal cortex was observed. From the activity of agonistic or antagonistic action of the ATII analogue, the usefulness of [Sar1, Ile8] ATII in making an etiological diagnosis of hypertension was discussed.