The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 71, 29-42, Copyright, 1940, by The Rockefeller Institute for Medical Research New York


ARTICLE

A CRYSTALLINE PRESSOR SUBSTANCE (ANGIOTONIN) RESULTING FROM THE REACTION BETWEEN RENIN AND RENIN-ACTIVATOR

Irvine H. Page M.D.1 and O. M. Helmer Ph.D.1

1 From the Lilly Laboratory for Clinical Research, Indianapolis City Hospital, Indianapolis

1. Renin reacts with renin-activator to form a strong pressor substance which is heat-stable, water- and alcohol-soluble, fluorescent, acid-stable, and alkali-labile. It is a reducing substance and is destroyed by strong oxidizing substances. It forms crystalline salts with oxalic and picric acids. The color reaction for arginine is the only one found to be strongly positive. It is suggested that this substance be called angiotonin.

2. Angiotonin produces a sharp, immediate rise in arterial pressure when injected intravenously. Pithing and dissipation of the anesthetic appear to increase the response. Tachyphylaxis occurs, in contrast to renin, only after many single doses.

3. The responses to adrenaline and angiotonin do not parallel one another. Cocaine, atropine, and stilbestrol do not affect the pressor action of angiotonin. Suprarenalectomy in brief experiments is also without effect.

4. Maximal amounts of angiotonin result when the proportion between renin and activator is roughly 3 to 100. This is not a stoichiometric relationship in the chemical sense. The temperature suitable for good yields is about 38°C., and the time of reaction from 10 to 20 minutes.

5. Renin destroys angiotonin when incubated with it.

6. Angiotonin causes marked contraction of intestinal segments of rabbits without reducing their rhythmic motion. It sensitizes the intestine to further doses of angiotonin and alters the intestine such that renin-activator contracts it. Angiotonin also constricts the vessels of a rabbit's ear perfused with blood or Ringer's solution.

Submitted on September 27, 1939


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