(7-Ile) angiotensin III: a relatively selective antagonist of angiotensin steroidogenesis

The effects of (7Ile) angiotensin III (AIII) and (1-Sar-8-Ile) angiotensin II (AII) on the pressor and steroidogenic effects of angiotensin were compared in conscious rats. (1-Sar-8-Ile) AII (500 ng/kg/min) equally inhibited the pressor responses of AII, AIII and (des-1-Asp) AI by 99% (P less than 0.0001) while (7-Ile) AIII (500 ng/kg/min) was without effect. The steroidogenic effects of AII, AIII and (des-1-Asp) AI (300 ng/kg/min) were inhibited by (1-Sar-8-Ile) AII by 83%, 69% and 50%, respectively, whereas (7-Ile) AIII inhibited their steroidogenic effects by 35%, 62% and 25%. respectively. In contrast, ACTH or potassium stimulated aldosterone release was not altered by either antagonist. In sodium depleted rats, (7-Ile) AII reduced the elevated serum aldosterone levels by 64% without altering the blood pressure, while (1-Sar-8-Ile) AII lowered the blood pressure without altering the concentration of aldosterone present in the serum. Thus, (7-Ile) AIII is relatively selective in its ability to antagonize the adrenal actions of endogenous and exogenous angiontensins when compared to the pressor actions of these peptides. Furthermore, these angiotensin antagonists appear to be useful as pharmacologic tools in assessing the characteristics of the angiotensin receptors in a particular tissue.