Stimulation of aldosterone production by angiotensin II peptides in vitro: enhanced activity of the (1-sarcosine) analogue.

The biological activity of angiotensin agonists has been determined in a highly sensitive in vitro assay system, based upon aldosterone production by isolated dog adrenal cells. The responses to angiotensin II and the heptapeptide [Des-Asp-1]-angiotensin II are identical, while the [Des-Asp-1, Des-Arg-2]-hexapeptide and the [Des-Phe-8]-heptapeptide are almost completely inactive. By contrast, [Sar-1]-angiotensin II, a potent agonist upon vascular smooth muscle, is also about 10 times more active than angiotensin II in stimulating the production of aldosterone by dog adrenal cells. The increased agonist activity of [Sar-1]-angiotensin II is attributable to increased binding affinity as well as increased efficacy at the adrenal receptor site. These results also suggest that conversion to the [Des-Asp-1] heptapeptide is not an important intermediate step in the action of angiotensin II upon the zona glomerulosa.