chemical factors in hypertension - ACS Publications

It is time, therefore, to examine the progress made during the past few .... For purposes of brevity, we will call this material the Hochdrwk- stoff. ...
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Humoral Pressor Substances and Their Relation to Arterial Hypertension HENRY A. SCHROEDER and NORMAN S. OLSEN

Downloaded by 190.138.250.224 on December 4, 2015 | http://pubs.acs.org Publication Date: January 1, 1949 | doi: 10.1021/ba-1950-0002.ch001

Department of Internal Medicine, Washington University School of Medicine, St. Louis, Mo.

Arterial hypertension, one of the most important diseases under modern social and economic conditions, presents a major problem to biochemistry: the discovery of specific therapeutic measures for its alleviation. This p a p e r discusses known humoral substances, examines each in the light of its possible relation to hypertension, and considers other evidence of the existence of such substances and their chemical structure. Humoral pressor mechanisms are p r o b a b l y initiated b y neurogenic ones and therefore comprise only one link in the chain of events that lead to chronic hypertension.

T h e discovery of specific therapeutic measures directed at arterial hypertension has become one of the major problems of biochemistry. T h e prevalence of this condition i n the modern social and economic environment has made it one of the most important diseases to which man is heir. It is time, therefore, to examine the progress made during the past few years i n the elucidation of the pathogenesis of this disease, especially those factors of biochemical interest. Arterial hypertension is very common. Approximately 4 0 % of the population over the age of 40 exhibit elevations of blood pressure, more than 140 m m . of mercury systolic and 90 m m . diastolic (64). T h e incidence increases with advancing years. It appears to be greater in negroes (2, 8, 28), the obese (83), and those exposed to higher degrees of civilization (16). T h e effects of chronic hypertension on the human organism are, with one exception, of little interest to the investigator studying pathogenesis, although of great import to the sufferer and his physician. T h a t exception is failure of the kidneys. Disease a n d failure of the heart are probably caused b y chronic overstrain, often associated with a n other metabolic disease, arteriosclerosis of the coronary arteries. T h e y account for about two thirds of the deaths primarily due to hypertension. Strokes of apoplexy, or cerebral vascular accidents, from rupture or thrombosis of a cerebral artery weakened b y disease cause another sixth, uremia about one twelfth, and other conditions the remainder (28). Except for uremia, these events are usually the result of overwork and increased arterial tension. Only rarely does the heart escape hypertrophy. Aside from major changes in organs, the only constant pathological findings concern the arterioles; their walls are thickened, the ratios of wall to lumen being increased. Degeneration of muscular coats, intimai thickening, and sometimes (in " m a l i g n a n t " hypertension) necrosis occur. These alterations are most marked i n the kidneys, but are found less constantly in most other areas. T h e evidence that arteriolar disease is secondary to, and is not the primary cause of, chronic hypertension is conclusive, although i n direct. Experimentally, similar lesions can often be produced i n the kidneys of certain animals (56, 67), when renal hypertension is induced. In the case of the dog, lesions a p 3

In CHEMICAL FACTORS IN HYPERTENSION; Advances in Chemistry; American Chemical Society: Washington, DC, 1949.

ADVANCES IN CHEMISTRY SERIES

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pear less readily, a n d special techniques must be used (52). I n almost half of a series of renal biopsies taken from hypertensive patients little or no arteriolar sclerosis was seen (11), whereas almost all the kidneys of such individuals show it at autopsy. Certainly, the nature of the lesions themselves suggest that they cause renal ischemia; although a result of hypertension, they probably contribute to its maintenance and further progress. Therefore, arterial hypertension m a y begin as a generalized physiological alteration in hemodynamics, producing secondary pathological changes i n arterioles. Sustained h y ­ pertension leads to cardiac hypertrophy and more renal arteriolar sclerosis. Finally, be­ cause of overwork, overstrain, and the frequent association of arteriosclerosis, the heart or brain is permanently damaged and death ensues. T h e duration of life from onset of h y ­ pertension to terminus is extremely variable (6 months to over 40 years). Psyche

Kidneys

Nerves

Blood Vessels Arteriolar Sclerosis

Downloaded by 190.138.250.224 on December 4, 2015 | http://pubs.acs.org Publication Date: January 1, 1949 | doi: 10.1021/ba-1950-0002.ch001

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