I. Pharmacology of Angiotensin Antagonists

Abstract
Several analogues of angiotensin II (ATII) have been characterized as antagonists against ATII and ATI, and compared with lidoflazine and guancydine, on the rat isolated stomach strip.The pA2 and pA10 values have been determined according to Schild (1947, Br. J. Pharmacol. 2, 189–206) after 5 and 15 min of contact of the antagonist with the tissue.The results show that (8-Gly)-ATII, (8-n-But)-ATII, (8-Val)-ATII, (8-Ile)-ATII, and (8-Leu)-ATII are specific and competitive antagonists of ATII and ATI, because the differences pA2 – pA10 are near to 0.95, the theoretical value for competitive antagonists. The same compounds do not influence the myotropic effect of 5-hydroxytryptamine (5-HT) or bradykinin on the same tissue. (8-Leu)-ATII and (8-Ile)-ATII are 12 times more active than (8-Gly)-ATII and the similarity of pA2 values for (8-Leu)-ATII and(8-Ile)-ATII to the pD2 value for ATII strongly suggests that one molecule of agonist is blocked by one molecule of antagonist. (1-Sar-8-Leu)-ATII is specific for ATII, but the antagonistic action of this compound is not of the competitive type (pA2 – pA10 = 0.65).PA2 – pA10 for guancydine and lidoflazine correspond approximately to 0.75. Myotropic action of 5-HT and bradykinin are antagonized by concentrations of guancydine and lidoflazine similar to those used to inhibit ATII and ATI. This suggests that guancydine and lidoflazine are noncompetitive and nonspecific antagonists of angiotensin.