The role of the catecholamines in hypertension: A review ∗

Abstract

T ODAY medullary adrenal tumors which contain varying increased amounts of epinephrine and norepinephrine are known to cause hypertension which is relieved when the tumors are removed surgically. The question now arises as to whether the catecholamines play a role in chronic essential hypertension of unknown etiology. The two catecholamines, epinephrine and norepinephrine, are produced in the chromafi tissue of the normal adrenal medulla or wherever chromaffin tissue is located in the sympathetic nervous system, the heart, and the brain. More recently, chromaffin tissue has been demonstrated around the nerves and blood vessels of the skin. In 1894, Oliver and SchZfer’ first demonstrated that intravenous administration of adrenal extracts to animals was followed by a pressor response, and the question arose as to the role of the adrenal gland in the pathogenesis of hypertension. In the following four years, Abel and Crawford,3 Aldrich3 and Takamine4 isolated crystalline epinephrine (adrenalin) from the adrenal gland. In 1904, Stolz5 synthesized both adrenalin and its amino homologue, noradrenalin. From 1905 to 1945 the work of various investigators including Elliott,6 Loewi,’ Cannon and Lisshk8 and Cannon and Uridilg led to the belief that adrenalin was the specific hormone of the adrenal gland as well as the neurohormonal transmitter of the adrenergic nerves. Because of some discrepancy between the effect of stimulation of the sympathetic nervous system and that of adrenalin, Cannon postulated the existence of two sympathins, E and I. In 1910, Barger and DalelO pointed out that there was a closer resemblance between the effects of stimulation of the sympathetic nervous system and those of noradrenalin, but this work was overlooked for many years, with only sporadic reports of similar observations. From 1945 to 1948, von Euler” and various other workers (Gaddum and Goodwin,12 Folkow and UvnW3) established that noradrenalin was the neurohormonal transmitter of the sympathetic nervous system and that both adrenalin and noradrenalin were the specific hormones of the adrenal medulla. Because of the possible role noradrenalin (norepinephrine) might play in the production of hypertension, and with the simultaneous introduction of new antihypertensive drugs, the biochemists, pharmacologists, physiologists and clinicians entered into the most extensive investigations to ascertain if possible the cause and the best treatment for hypertension. From 1925 to the late 1940’s, patients with hypertension were treated with a wide variety of operations on the sympathetic nervous system. Adson,l* in 1924, introduced the limited bilateral lumbar sympathetic ganglionectomy. During the ensuing period, the most widely used procedure was the thoracolumbar sympathectomy of Smithwick and Thompson,15 in which the ganglionectomy extended from Tb-9 to Ll-2. In 1939, Grimson”j carried out total sympathectomies. This latter method carried a high mortality and morbidity. However, sympathectomy demonstrated that it was possible to lower the blood pressure permanently in many cases of essential hypertension and to normal levels in some. This was accomplished by interfering with vasoconstrictor reflexes involved in certain homeostatic adjustments of the circulation, especially those which come into