Comparison of two angiotensin II analogues in normal subjects and hypertensive patients

Two angiotensin II analogues, i.e., 1-sarcosine, 8-isoleucine angiotensin II (Sar1, Ile8-AII) and 1-sarcosine, 8-alanine angiotensin II (Sar1, Ala8-AII), are now available in the clinical study. Comparative studies of the antagonistic potency and the agonistic effect of these two AII analogues were made in normal subjects on three sodium balances and in hypertensive patients with various etiologies on sodium depletion. Both AII analogues had an agonistic pressor effect in normal subjects. This effect changed with different sodium balances. In the low sodium state, this agonistic action was minimized. The agonistic pressor effect of Sar1, Ile8-AII was greater than that of Sar1, Ala8-AII in all sodium states. There was found an agonistic activity of both AII analogues not only on blood pressure, but also on renin and aldosterone secretion, and renal vasculature in normal subjects on a regular diet. The antagonistic depressor potency of both compounds was also varied by changing sodium balance, being greatest in the low sodium state. In hypertensive patients on sodium depletion, the blood pressure responses of individual patients to these two AII analogues were significantly correlated (r = 0.8, n = 20). These results indicate taht pretreatment of sodium depletion is necessary to prevent the side effect caused by the agonistic pressor action of AII analogue, and also to predict renin depency in hypertensive patients efficiently.