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I Indomethacin had an equal inhibitory effect on the response of the guinea-pig isolated ileum to angiotensin II (angiotensin), bradykinin, histamine and acetylcholine. This effect did not seem to result from inhibition of prostaglandin synthesis, as it did not depend on the time of treatment with indomethacin. 2 Prostaglandin E2 (prostaglandin) potentiated the responses of the guinea-pig ileum to angiotensin, bradykinin, histamine and acetylcholine without significant differences in the effects observed.3 In the rabbit isolated mesenteric and coeliac arteries, indomethacin had an equal potentiating effect on the responses to angiotensin and to adrenaline. In these organs pre-incubation with indomethacin was necessary for the effect to be observed, and this effect lasted for 2 h or more after that drug was removed from the medium. 4 No cross-tachyphylaxis between angiotensin and adrenaline was observed in the rabbit mesenteric and coeliac arteries.5 It is concluded that the effects of indomethacin and prostaglandin on the response of the guinea-pig ileum to the four agonists result from an action on the smooth muscle contractile mechanism per se rather than from an inhibitory action on the release of endogenous prostaglandin produced by the four agonists. 6 The results with the rabbit isolated arteries indicate that tachyphylaxis to angiotensin in these organs is not caused by prostaglandin release.

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An alkylating analogue of angiotensin II (AII) containing a nitrogen mustard group (p-[N, N-bis(2-chloroethyl) aminojphenylbutyryl at the N-terminus ([Chi¹]-All) was shown to be an irreversible specific inhibitor of the action of AII on the isolated rat uterus. The inhibition was observed when the Ca⁺⁺ concentration in the medium was 0.18 mM, and was more intense in calcium-free medium. It was not observed in the presence of 1 mM Ca⁺⁺. It is concluded that a site near (but not on) the AII receptor is alkylated by [Chi¹ ]-AII, and the properties of this site suggest that it is the same one involved in the phenomenon of tachyphylaxis.