The Mosaic Theory of Arterial Hypertension—: Its Interpretation

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume io · Number 3 · Spring 1967 THE MOSAIC THEORY OF ARTERIAL HYPERTENSION —ITS INTERPRETATION IRVINE H. PAGE, M.D* Forty years ago when I was a medical student, the diseases wc studied were quite different from those of today. If we knew syphilis, tuberculosis , pneumonia, typhoid fever, malaria, and cancer, we thought we had mastered all that were truly important. Arteriosclerosis was believed to be merely a result ofaging, and hypertension was possibly a disease, but then possibly not! Most clinicians thought it to be a compensatoryphenomenon to force blood through thickened arteries. To lower blood pressure was to court the disaster ofuremia because the kidneys would receive insufficient blood. In a way, this was a convenient theory because we had no idea of how to lower blood pressure! Research into the nature of either hypertension or atherosclerosis had been desultory. True, in 1898 the Swedish physiologists, Tigerstedt and Bergman, had shown that extracts ofkidneys raised blood pressure when injected intravenously into rabbits. They had the shrewd good sense to christen this extract "renin" many years before it had been identified or purified. I suspect that few investigators ever got more "mileage" out of one paper than they did. It was, indeed, a good paper, but not that good! There were attempts to produce reliable experimental counterparts of hypertension in animals. Various methods for producing renal hypertension were found, and a very impressive one for neurogenic hypertension was demonstrated. In 1908 Ignatowski developed atherosclerosis in rabbits by feeding them rriilk and egg yolks, and in 1914 Anitchkow found that * Research Division, Cleveland Clinic Foundation, Cleveland, Ohio. 325 feeding cholesterol alone did the same. Despite this good work, by 1930 there was little progress or excitement in either field. But about that time a feeling was growing that infectious disease might be conquered. I well remember the first talk by Leonard Colebrook on the treatment ofpuerperal sepsis with sulfanilamide. I was dubious, but within the year this chemical and its derivatives, such as sulfapyridine, were found to be much more valuable than we had any right to suppose. Infections were about to lose their ascendancy. The "Captain of the Men of Death" was no longer pneumonia or tuberculosis. The next decade saw the introduction of antibiotics which, except for viral infections, pretty well sealed the fate ofa major portion ofmicroorganismal disease. In a matter of only a few years, atherosclerosis and hypertension emerged as the major killers. The two now constitute the bulk ofthe 53 per cent ofpersons dying from heart disease and stroke in this country— this despite the fact that only a few decades before, neither disease had any serious currency in either medical thinking or teaching. I recall in 1932 giving a talk in Philadelphia on the nature ofatherosclerosis which, because oflack ofcontent and current interest, might as well have been on quantum mechanics. And again I was brash enough to speak before the New York Academy of Medicine in 1937 on "The Nature of Hypertension," an ambitious title, to say the least. Even the doctor sitting next to my young and beautiful wife went to sleep! My own interest had been stimulated in medical school in 1924 by Dr. James Ewing's interest in toxemia ofpregnancy and nephritis. But it was not until 1930, after a stint on brain chemistry, that I returned to the problem. On my way back from Germany tojoin Dr. D. D. Van Slyke, I spent some time with Volhard in Frankfurt. There I was shown a bottle containing powdered renin and introduced to Volhard's notions about the mechanisms of what he called "white" or "pale," and "red" hypertension , that is, renal hypertension and essential hypertension. Volhard's physiology and biochemistry were sadly lacking, but his clinical perceptiveness certainly was not. This period then was the prelude to a drastic change in the nature of medical practice, a change that has not yet sunk into the resistant crania of many medical students and their teachers. Even today the nature and treatment of hypertension and atherosclerosis are miserably taught in most medical schools, and this is reflected in the equally dismal discussions 326 Irvine H. Page · Theory ofArterial...