THE CAUSE OF ESSENTIAL HYPERTENSION MILTON MENDLOWITZ, M.D., STANLEY GITLOW, M.D., and NOSRAT NAFTCHI, M.S.* When the blood-pressure cuffwas discovered about sixty years ago, it became apparent to many workers in Europe and in this country (1-4) thathigh blood pressure was a common affliction ofthe adulthuman being which not infrequently caused his death, either directly or indirectly. It could cause a blood vessel to burst in the brain, produce progressive deterioration ofthe kidneys, cause the heart to fail, or accelerate the process of arteriosclerosis. Arteriosclerosis, in turn, could lead to vascular occlusions , especially in the heart, brain, or extremities, and so hasten the end. Through the years many causes have been propounded for this disease, including psychic disturbance (5), endocrine imbalance (6), hereditary predisposition (7), neurovascular dysfunction (8) (initiated, for example, by the carotid sinus), renal malfunction (9), etc. When the smoke ofcontroversy had cleared a little, some hypertensive diseases, such as those associated with adrenal medullary tumors (10) and adrenal cortical tumors or hyperplasia (11) and those associated with such renal diseases as acute and chronic glomerulonephritis, chronic pyelonephritis, and polycystic kidneys, were distinguished from primary hypertension itself, although even today this distinction cannot always be made clinically in the individual patient. When neurogenic hypertension was produced in the laboratory by section of the aortic depressor and carotid sinus nerves of dogs (12) and when renal hypertension was produced by interfering with the canine renal arterial circulation (13), opposite schools ofthought developed. One identified primary hypertension as essentially renal, the other believed it to be essentially nervous in origin. However, tissue examined directly by biopsy or at autopsy revealed no renal abnormality early in the course of * Department ofMedicine, Mount Sinai Hospital, New York. This work has been aided by grants from the American Heart Association and the National Heart Institute (H-Ï164). 354 M. Mendlowitz, S. Gitlow, and N. Naftchi · Essential Hypertension Perspectives in Biology and Medicine · Spring 1959 human primary or essential hypertension (14). Even if the hypertension were attributed to such renal ischemia, some mechanism would have to be invoked to account for the initiation of the localized ischemia. Moreover , the nature of the hypertension produced by renal ischemia was elusive to the investigator. Pressor substances isolated fromthekidneywere presumed responsible for this renal hypertension (15, 16). Then it was difficult to explain the occurrence ofhypertension when both kidneys were ablated (17), so electrolyte retention or a substance elaborated by normal kidneys which prevented hypertension was postulated. It was also suggested that retention of water and electrolytes was not generalized but was confined to small blood vessels, especially arterioles (18, 19), and that the subsequent development ofarteriolar sclerosis provided the final impetus toward increased peripheral resistance. Thus, it was customary about ten or fifteen years ago to say that the cause ofessential hypertension was unknown. Now some workers in the field believe that primary hypertension has many causes—sometimes renal, sometimes endocrine, sometimes hypothalamic, sometimes a combination, etc. Ifthat state ofmind is reassuring, several observations are not. For example, it has become quite clear that primary hypertension is hereditary (7, 20), although how the predisposition is implemented is unclear. Is it via the kidneys in some cases, the blood vessels in some, the nervous system in some, and the endocrine glands in still others? This seems unlikely from what is known ofhereditary disease. Also, sympathectomy and therapy with drugs directed at neurogenic vasoconstriction have been so dramatically effective in many cases that it seems as though increased neurogenic vasoconstriction must be involved in primary hypertension. The fact that equivalent drug dosage has a greater depressor effect in hypertensive than in normotensive subjects (21) supports this feeling. On the other hand, salt depletion by the low-sodium diet (19) and presumably by such diuretics as chlorothiazide (22, 23) seems to act either by increasing the caliber ofblood vessels or by decreasing blood flow, as measured in both instances after inhibition ofsympathetic neural vasoconstriction. Also, some recent evidence suggests that chlorothiazide decreases vascular sensitivity to norepinephrine (24). It is disturbing, however, that ganglion-blocking drugs, particularly, decrease blood pressure not only by inhibiting neurogenic arteriolar vasoconstriction but also by decreasing cardiac output, possibly because...
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Nov 1, 1981
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