Clinical Applications of Synthetic Angiotensin Ii Analogue

[1-sarcosine, 8-isoleucine] angiotensin II ([sar1 ile8] A II), one of the synthetic angiotensin II analogs, is a potent and 'long-lasting angiotensin II antagonist, whose competitive antagonism against pressor action of angiotensin II has been demonstrated in laboratory animals. Herein preliminary results of clinical applications of this compound were presented. There were no appreciable changes in urinalysis, complete blood counts and other routine laboratory tests, 6 and 24 hours after i.v. administration of 0.25mg [sar1, ile8] A 11 in 5 normal men. Transient elevation of blood pressure was observed after i.v. injection of 0.25mg for five minutes but not after i.v. infusion of the same dose for 30 minutes. Dose-related blockade of angiotensin II induced hypertension. was seen by concomitant administration of [sar1, ile8 J A II. The anti-angiotensin 11 action of [sar1 ile8 J A 11 became manifest in 5 minutes after the initiation of [sar1, ile8] A 11 infusion and lasted as long as 1 hour after the cessation of the infusion. The effect of this compound was tested in selected kinds of human hypertension. No reduction of blood pressure was observed in 6 subjects with essential hypertension. One subject with malignant hypertension and one with angiography-proved unilateral renovascular hypertension showed more than 20mmHg reduction in both systolic and diastolic blood pressure, whose duration of hypertension was estimated to be less than one year. Seven other hypertensive subjects, renovascular or malignant, showed negative response and one other subject with renovascular hypertension showed intermediate response to [sar1, ile8] A II. It appears that [sar1, ile8] A 11 per se does not have property of reducing blood pressure and that it reduces blood pressure by conuteracting angiotensin II. It is suggested that angiotensin 11 is involved in the development and/or main-tenanee of human hypertension at least of relatively short duration, acompanied by elevated plasma renin activity.