Book Reviews

MECHANISMS OF HYPERTENSION: WITH A CONSIDERATION OF ATHEROSCLEROSIS. By Henry Alfred Schroeder, M.D., Springfield, Ill., 1957, Charles C Thomas, 379 pages. Price $9.00.

In the first half of this monograph Dr. Schroeder presents his current views on the mechanisms responsible for the initiation and evolution of primary hypertension. He accepts heredity as one of the basic predisposing factors and believes that the characteristic which is inherited is “a tend- ency to react to stress by vasospasm.” On the basis of the assumption that hypertension is largely confined to civilized people, it is suggested that the environmental stresses which initiate the disease in predisposed individuals are those which are inherent in an industrialized society. The existence of a specific defect of personality in hypertensive individuals is regarded as not clearly established, but it is conceded that there are important emotional factors in the disease which may be either primary or secondary.

The consensus of the conflicting evidence in the literature is judged to be strongly in favor of the hypothesis that the “vasospasm” which occurs during the early stage of intermittent or highly variable hypertension is mediated through overactivity of the sympathetic nervous system. In the later stages of the disease these neurogenic factors are gradually replaced by other mech- anisms which are capable of maintaining more or less permanent vasospasm. On the basis of a review of the evidence which has been adduced in support of various hypotheses concerning the nature of these perpetuating mechanisms, it is concluded that the most important are those which originate in the kidneys as a result of renal ischemia induced by neurogenic vasoconstriction.

Several ways in which renal ischemia might give rise to a generalized pressor effect are dis- cussed; for example, inhibition of amine oxidase might be expected to increase the amount of circulating pressor amines. This is an attractive hypothesis, but the author rejects it on the grounds that the concentration of pressor amines detectable in the blood of hypertensive patients is too low to explain the observed increase in peripheral resistance. It is considered possible, however, that inhibition of amine oxidase might decrease the rate of destruction of certain pressor polypeptides of renal origin, such as hypertensin and pherentasin.

Another group of hypotheses concerning the nature of nephrogenic pressor mechanisms is based on the ability of hydralazine to lower the blood pressure of hypertensive patients and the assumpton that it may do so by virtue of its known ability to bind heavy metals. In an attempt to suggest a mechanism whereby metal binding might produce an antihypertensive effect, evi- dence is cited to show that there is a progressive increase with age in the concentration of certain abnormal trace metals in the tissues of Americans, but not in those of primitive peoples.

It is suggested, for example, that accumulation of cadmium in the kidney might replace an essential trace metal in a metalloenzyme such as dihydroxyphenylalanine decarboxylase or mon- amine oxidase, with resulting inhibition of the enzyme. If one assumes that the inhibition of these or other enzyme systems is a mechanism whereby hypertension is sustained, the antihypertensive action of hydralazine could be explained on the basis of its ability to reverse the inhibition by chelating the abnormal trace metal.

An even more speculative hypothesis which is discussed in several places in the book is the possibility that a localized deficiency of vitamin Bs might be produced in the kidney as a result of interference with an essential trace metal by an extraneous one, even in the absence of signs of a general deficiency in the body as a whole. The only evidence cited in favor of this hypoth- esis is the fact that an elevation of blood pressure can be produced in young rats by administration of a vitamin Bg antimetabolite.

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150 BOOK REVIEWS Am. Heart J.

July, 1958

The role of the adrenals in the pathogenesis of hypertension is discussed briefly, but the author does not believe that overactivity of the adrenal cortex occurs in the great majority of cases of hypertension. He dismisses the finding of increased amounts of aldosterone in the urine of some hypertensive patients as merely an example of secondary aldosteronism due to some defect in the handling of sodium by the kidney.

The chapter on the pathogenesis of atherosclerosis is included partly because of the impor- tance of coronary and cerebral atherosclerosis as a cause of death in hypertensive patients, and partly in order to present the hypothesis that abnormal trace metals and a deficiency of vitamin Bs may be important pathogenetic factors in atherosclerosis as well as in hypertension. Since a deficiency of pyridoxine has been shown to cause damage to subintimal mucopolysaccharides in the monkey, it is postulated that a “conditioned” deficiency of vitamin Bb localized in the vessel wall might be a factor in the initiation of human atherosclerosis. On the basis of experiments in rats, a deficiency of vitamin B, might also be expected to favor the development of atherosclerosis by interference with the desaturation of fatty acids. It is also suggested that the accumulation of abnormal trace metals, chromium for example, might exert an atherogenic influence by stimulating the formation of cholesterol and fatty acids in the liver.

The last chapter in the book describes a proposed regimen for the treatment of atherosclerosis which is based on the above concepts of pathogenesis. The method includes the use of a diet which is low in animal fats and in saturated fatty acids generally, and which is high in unsaturated fats, especially linolenic acid. In addition, the patient is given a daily dose of 5 or 10 mg. of vitamin Bg and 0.5 Gm. of the chelating agent, calcium Versenate, to remove any abnormal trace metals which may be present. It is admitted that this form of therapy has not been employed long enough to permit evaluation of its effectiveness, but the early results are said to be encouraging. There is also a chapter on the treatment of hypertension which merely summarizes Dr. Schroeder’s previously published experience with the intensive use of the combination of ganglionic blocking agents and hydralazine.

The author’s admitted objective in writing this monograph is to put forward hypotheses which he believes to be in accord with the existing evidence, in the hope that they will stimulate controversy. In order to do this, much evidence from the literature has been accepted at its face value without critical examination of its validity, and in many instances support for a given hypothesis has been drawn from experimental observations whose relevance to the problem under discussion is distinctly limited. Nevertheless, all those who are engaged in the study of the patho- genesis of hypertension will find this monograph full of thought-provoking speculations concerning the interplay between some of the little understood physiological and biochemical factors which may be involved in the regulation of the blood pressure.

K. A. E.

L’ANNEE CARDIOLOGIQUE INTERNATIONALE, TOME V (The International Yearbook of Cardiology, Vol. V). Edited by Camille Lian, Paris, 1956, Expansion Scientifique Franyaise, 374 pages.

This fifth volume in its series assembles 24 articles written by French and other European cardiologists and is edited by Professor Camille Lian. It would not be practical to review each article, but as a whole the volume is a useful one which rewards the reader with precise informa- tion on a variety of subjects. Some of the articles merit special mention: “Pregnancy and Car- diopathies in 1955,” by P. Broustet, of Bordeaux. “Abnormalities of the Pulmonary Arteries

in Cases of Mitral Stenosis Due to Undergo Commissurotomy,” by G. C. Dogliotti, of Turin. “The Late Results of Mitral Valvulotomy,” by E. Coelho and J. F. DaCosta, of Lisbon. “The U Wave of the Clinical Electrocardiogram,” by Max Holzmann, of Zurich. “Ebstein’s Syn- drome,” by M. Mauquin, of Paris. “The Direct and Indirect Effects of Salicylate Therapy,”

by Jacques Roskam, of Liege. “Primary Pulmonary Arterial Hypertension,” by P. Soulie, of

Paris. This book offers an excellent view of the evolution of cardiology in Europe. Professor Lian

deserves much credit for his wise editorial guidance. This book is highly recommended to all

interested in cardiology. I-I. s.