Tachyphylaxis to angiotensin and some analogues has been demonstrated on spirally cut arterial strips from cat, dog, sheep and rat, and on venous strips from rabbit and cat. Rabbit and guinea pig arteries do not appear to become tachyphylactic. A free C-terminal carboxyl group of angiotensin is necessary for binding with receptor sites and development of tachyphylaxis. Tachyphylaxis seems to represent saturation of receptor sites. It can be reversed by plasma fractions rich in angiotensinase A, possibly by metabolizing the N-terminal part of angiotensin directly from the bound state. Dowex 50 can also reverse it, probably by physical adsorption and stronger binding of angiotensin. Angiotensinase A does not metabolize βaspartyl 1 -angiotensin and does not reverse tachyphylaxis to this peptide. A possible scheme of interaction between peptide and receptor site is presented.

An analog of angiotensin II, [Sar(1), Ile(8)]-angiotensin II, has a potent and long-lasting competitive antagonistic effect against angiotensin II when tested for its myotropic action on the isolated rabbit aorta and for its effect on blood pressure in anesthetized cats and dogs. Compared to [Ile(8)]-angiotensin II, the new analog has equal antagonistic potency on the isolated system but a much greater potency in vivo. It is assumed that sarcosine in position 1 protects the peptide against enzymatic degradation and enhances its half-life. This study demonstrates that the modification in both positions 1 and 8 are important for the in vivo antagonistic potencies of angiotensin analogs.

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The effects of histamine and 4-methylhistamine (a selective H₂-agonist) were studied on the isolated rat stomach fundus and rabbit aortic strips superfused with Krebs’ solution. The contraction induced by histamine was found to be mediated via mepyramine-sensitive H₁, while the relaxation induced by the amine through metiamide-sensitive H₂-receptors in both smooth muscles. Prior addition of metiamide to the superfusion medium caused an apparent dose-related potentiation in the response to histamine on the aortic strip but not on the stomach fundus strip. The relaxation produced by histamine on the aortic strip demonstrated when the muscle was pretreated with mepyramine and contracted by angiotensin II or serotonin. Metiamide competitively inhibited the relaxation induced by histamine but not by papaverine in both smooth muscles. 4-Methylhistamine produced only a relaxation in the rat stomach fundus which could be competitively inhibited by metiamide. This analog had no agonistic property in the aortic strip. From these results it was concluded that histamine H₁- and H₂-receptors are present in both smooth muscles. The predominant contractile effect of histamine is mediated through H₁-receptors and the relaxing effect of the amine through H₂-receptors.

Interaction of histamine and a new histamine H₂-receptor blocker, burimamide, was studied in the isolated perfused guinea-pig lung. Histamine induced a rise in perfusion pressure when the lung was perfused with Krebs’ solution. This pressor response was reversed to a depressor effect when mepyramine, H₁ -receptor blocker, was added to the perfusing medium. Burimamide competitively antagonized the depressor effect of histamine in the pulmonary vessels. Prior treatment of pulmonary vessels with burimamide alone caused an increase in histamine-induced perfusion pressure. These results suggest that the depressor effect of histamine on pulmonary vascular bed of guinea pig is mediated through the H₂-receptors.