BLOCKADE OF THE EFFECTS OF ANGIOTENSIN, OXYTOCIN, NOREPINEPHRINE, 5-HYDROXYTRYPTAMINE AND ACETYLCHOLINE BY GUANCYDINE

¹ Centre de Recherches sur l'Hypertension Arterielle, Hôpital Broussais, Paris, France

The hypotensive effects of guancydine (1-cyano-3-tert.-amylguanidine) were attributed by Cummings et at. (J. Pharmacol. Exp. Ther. 181: 88-97, 1968) to a "semi-selective" blockade of angiotensin activity. That concept is tested further in this paper. The contractile responses of the rat uterus and colon were tested in a low Ca (0.6 mM) Krebs' solution in order to avoid spontaneous contractions. Rabbit aortic strips were suspended in normal Ca (13 mM) solution. The agonists used were angiotensin amide (valyl-5-angiotensinamide II) on colon, uterus and aorta; oxytocin on uterus; 5-hydroxytryptamine on uterus; acetylcholine on colon; and norepinephrine on aorta. When used in concentrations higher than 10^-4 M, guancydine blocked the responses to all of these agonists in a noncompetitive fashion. In another series of experiments, uteri and colons were suspended in a high Ca (2.5 mM) Krebs' solution. In this solution, the organs developed strong rhythmic activity; guancydine in concentrations higher than 10^-7 M inhibited the spontaneous contractions. Guancydine, 5 x 10^-4 M, inhibited the effects of oxytocin on net water influx of frog's (Rana esculenta) bladder epithelium.