Pressor substances

It is comforting to hear Beyer say that the various concepts of the etiology of essential hypertension are not mutually exclusive and that a combination of these theories may be the correct idea. He, too, agrees that the initial vasoconstriction is probably motivated by autonomic impulses, with the release of pressor substances that induce the development of vascular disease in the kidneys and other organs. The weakness of Beyer s concept is that there is no unequivocal proof that hypertension per se produces arteriosclerosis. Even in the hypertension associated with pheochromocytoma, for example, the development of vascular disease in the kidneys or other organs, as a direct result of the hypertension, has not been established. 

Humoral Pressor Substances and Their Relation to Arterial Hypertension... 

The hypertension itself damages renal arterioles, which become hypertrophied and narrowed. Thus, organic renal ischemia results, in itself causing continuous production of pressor substances. 

Table I. Pressor Substances Possibly Related to Hypertension9...

The three protein pressor substances are renin, a prolonged pressor substance found in shock, and vasoexcitor material. Apparently they are different substances. Renin is the best understood (10). Its reaction with a globulin substrate to form hypertensin or angiotonin suggests that it is a proteolytic enzyme. Renin has been considerably concentrated, but has not been purified. The stimulus for its release by the kidney is a reduction of renal blood flow just how this comes about is unknown. 

A crude pressor substance was obtained from the anaerobic autolysis of renal tissue by Victor et al. (65), which was inactivated by tyrosinase (53) and amine oxidase. It probably contained isoamylamine, phenylethylamine, and tyramine (17) released by proteolytic enzymes. Pressor substances were not formed or were destroyed under conditions of aerobiasis. It is difficult to apply these results to in vivo pathological states except under extreme anoxia and necrosis of renal tissue. 

An unidentified substance, named nephrin, was described by Enger (19). Nephrin is a pressor material having a prolonged action, obtained from extracts of renal cortex, but not present in any other tissues. It was also found in urine and in blood and was said to have been present in increased amounts both in hypertensive dogs and in patients with hypertension, eclampsia, nephritis, and other hypertensive conditions. Its action was not intensified by cocaine nor affected by ergotoxin and it did not act upon the guinea pig uterine muscle. As it was dialyzable, it probably was not renin. If this work is substantiated, nephrin represents yet another renal pressor substance probably of nonprotein nature. Its relation to hypertension has not been substantiated. 

An interesting reaction to intradermal histamine has been described (55), which, while not a pressor substance, appears to reproduce certain symptoms and signs encountered in hypertensive subjects. Histamine has a renal action similar to epinephrine (47), constricting efferent arterioles. In neurogenic hypertensive patients it also produces the hypertensive diencephalic syndrome." Whether this reaction is direct, or indirect through some other mechanism, is obscure. 

By the use of specific enzymes, studies have been made in an attempt to classify the pressor substances in experimental hypertension. If a specific enzyme lowered blood pressure in hypertensive animals and not in normal ones, it was assumed that the substrate of that enzyme was attacked, and therefore contributed to the hypertension. Such assumptions, while not wholly valid, nevertheless pointed to certain substances as possibly concerned in hypertension. 

The renal pressor mechanism—renin and hypertensin—acts in acute hypertension and in acute renal ischemic states, but apparently not in chronic hypertension. The other mechanisms shown to be active in chronic hypertension are vasoexcitor-vasodepres-sor material relationship pherentasin, a pressor substance found only in human hypertension amines resulting from the insufficient oxidation of amino acids, which are increased in human hypertension and norepinephrine (Sympathin E), which largely reproduces the hemodynamic picture of chronic hypertension. Most of the known pressor substances, with the notable exception of norepinephrine, come from disturbances of, or are extracted from, the kidneys. The large number of pressor substances which have been obtained suggests that many may represent different stages of metabolism of certain parent substances, and that their effectors may be fewer in number and simpler in structure. The chemical identification and purification of most of these substances leave much to be desired, and their phafmacology has in most cases been inadequately studied. The whole problem, however, may soon become simplified. 

DRURY—DISCUSSION OF PAPER ON HUMORAL PRESSOR SUBSTANCES... 

There is no dearth of chemical compounds that will cause a rise in blood pressure when injected into the experimental animal. Extracts of plant and animal tissues yield several, and enzymes present in the tissues will often produce pressor substances as a result of autolysis. For a chemical agent then to be proved as a cause of hypertension it must be found as such in the animal and in greater amount in the hypertensive than in the normal animal. The substance must be capable of producing a continued elevation of blood pressure when administered continuously to the normal animal. The substance must be of such a nature that the body does not make corrective or adaptive responses to it. In this fashion tachyphylaxis or immunological reactions may reduce the action of certain agents if given repeatedly. 

This same qualitative difference between adrenaline and noradrenaline obtains for the splenic artery/splenic vein equipressor dosage-response ratios as well, and both observations quite possibly may find their explanation in the recent work of Euler (64-70). He has found that the pressor substance isolated from the heart, blood, liver, and spleen has predominantly the characteristics of noradrenaline. Thus, he has considered Sympathin E to be identical with Z-noradrenaline. 

Page, I. H., and Helmer, O. M. 1940. A crystalline pressor substance (angiotonin) resulting from the reaction between renin and renin-activator. J Exp Med 71 29-42. 

MAO Inhibitors and Tyramine. There have been reports of serious reactions (e.g., hypertensive crises) occurring in patients being treated with a MAO inhibitor following ingestion of foods with a high content of pressor substances, such as tyramine. 

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