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Comparative receptor-binding properties of heptapeptide and octapeptide antagonists of angiotensin II in rat adrenal glomerulosa and uterine smooth muscle.

Pharmacological studies in the rat and other species using angiotensin II (Ang II) antagonists suggest that the structural requirements of Ang II antagonists differ in smooth muscle and adrenal target tissues. Specifically, heptapeptide antagonists preferentially inhibit steroidogenic responses to Ang II, while octapeptide antagonists preferentially inhibit pressor responses to Ang II. We have compared the ability of a number ofhepta- and octapeptide antagonists to inhibit [125I]iodo-Ang II receptor binding in rat uterine smooth muscle and adrenal target tissues. The purpose was to determine whether variable receptor-binding affinities in these tissues could account for the differences observed in vivo. A number of similarities was noted in the two target tissues. First, each of the octapeptide antagonists was a more potent inhibitor of Ang II binding than its corresponding 2–8 heptapeptide antagonist. Second, there was a linear relationship between the dose ratios of receptor binding in the adrenal and i...