Effect of three angiotensin II antagonists, [Sar1, Thr8]-, [Sar1, Ile8]-and [Sar1, Ala8]angiotensin II on blood pressure and endocrine factors in normal subjects

Abstract

The biological effects of 1-Sarcosine, 8-Threonine angiotensin II ([Sar1, Thr8]ANG II) on blood pressure, plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were investigated in six normal subjects on an unrestricted diet, and compared with those of 1-Sarcosine, 8-Isoleucine ANG II ([Sar1, Ile8]ANG II) and 1-Sarcosine, 8-Alanine ANG II ([Sar1, Ala8]ANG II). All three ANG II analogues (AIIA) showed agonistic pressor activity, that of [Sar1, Ile8]ANG II being greater than that of [Sar1, Thr8]ANG II or [Sar1, Ala8]ANG II. The antagonistic effect of [Sar1, Thr8]ANG II on blood pressure was less than [Sar1, I1e8]ANG II or [Sar1, Ala8]ANG II. Both [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II increased PAC and blocked the steroidogenic action of ANG II, while [Sar1, Thr8]ANG II showed little effect on PAC. All three AIIA caused similar suppression of PRA and showed no inhibitory effect on the decrease in PRA produced by ANG II. These results indicate that [Sar1, Thr8]ANG II is an AIIA with weak agonistic pressor action and that it has vascular selective properties. It is also suggested that ANG II receptors in a variety of target organs are heterogeneous.