A Crystalline Pressor Substance (Angiotonin) Resulting From the Reaction Between Renin and Renin-Activator

Abstract

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.

The angiotensin II type 1 receptor and receptor-associated proteins

“…Renin was a central subject of intense investigation because of its role in blood pressure regulation before the discovery of angiotensinogen. Early studies by two groups, led respectively by Page and Braun-Menendez, independently demonstrated that renin was not the direct cause of experimental hypertension, but rather it acted on a substance in plasma to yield a heat-stable peptide possessing both pressor and vasoconstrictor functions [1], [2].…”

The Hemodynamic Effects of Angiotonin in Normal Man 1

“…Angiotonin, a pressor substance arising out of the reaction between renin and renin-activator, has been suggested by Page and Helmer (1) as the humoral mediator of clinical and experimental hypertension. The vasopressor activity of this substance in animals is not abolished by anesthesia or pithing; it causes vasoconstriction in the isolated rabbit's ear (1) and reduces the renal blood flow by constriction of the efferent glomerular arterioles (2), facts which lead to the belief that it acts directly on the peripheral vascular bed.…”

“…The vasopressor activity of this substance in animals is not abolished by anesthesia or pithing; it causes vasoconstriction in the isolated rabbit's ear (1) and reduces the renal blood flow by constriction of the efferent glomerular arterioles (2), facts which lead to the belief that it acts directly on the peripheral vascular bed. It is also known that it decreases the diastolic volume in the isolated mammalian heart (3).…”

The Goldblatt memorial lecture. Part I: Experimental renovascular hyptertension.

“…Whether the sustained hypertension is due to the salt and water retention and increase in plasma volume, or to the reduction in concentration of vasodilator agents, such as bradykinin or prostaglandins, or to the release of vasoconstricting agents other than renin as proposed by Grollman, and KrishmanAmerty* 7 by Skeggs et al M and by Boucher et al' 9 is not yet established. Riegger and the other members of the Glasgow group," however, have proposed that angiotensin II is responsible for the initial rise in systemic pressure and for the sustained hypertension in sodium-replete dogs.…”