Direct Effect of Adrenal Cortical Hormone upon Blood Pressure in Shock Induced by Intestinal Manipulation

Abstract

The writers have repeatedly called attention to the slow but steady decline in blood pressure which occurs in adrenalectomized dogs after withdrawal of cortical hormone, and have pointed out that following administration of hormone to animals prostrate from adrenal insufficiency the rise in arterial pressure from shock levels to normal is one of the first and most dramatic changes observed during recovery. The fall in pressure is not a terminal event but is one of the earliest changes from normal exhibited by the animal not receiving hormone. During the past year we have performed 4 different types of experiments on adrenalectomized dogs, the results of which show that the cortical hormone exerts a direct effect upon blood pressure which is distinct and separable from the action of this hormone upon blood volume, and fluid and electrolyte distribution. Table I gives the essential data obtained from a representative case in one type of experiment in which intestinal stripping was used to induce shock. Dogs lacking adrenals do not spontaneously raise their lowered blood pressure or recover from this treatment. Seven active, vigorous, adrenalectomized dogs kept for one year in the laboratory on maintenance doses of cortical hormone, were used. The hormone was withheld 18 hours previous to use in the experiments. The animals were in normal health, at peak weight, and revealed no deviations from normal in their blood and urine chemistry, water balance and arterial pressure. They were etherized and a portion of the small intestine vigorously stripped through the fingers for 20-30 minutes. The dogs recovered rapidly from the anesthetic and their activity and vigor appeared undiminished. However, within the ensuing 6-12 hours the arterial pressure declined to shock levels—40-50 mm. Hg. When the dogs were at the point of collapse they were injected intravenously with 3 cc. per kg. body weight of hormone. The arterial pressure slowly but steadily rose and attained the normal level within 36-48 hours. All shock symptoms disappeared and activity and vigor returned. Arterial pressure increases of as much as 5-10 mm. Hg. per hour were not infrequently observed during the first hours following hormone injections. Study of the serum Na, Cl and K showed negligible changes in concentration of these electrolytes. In general the Na and Cl tended to increase slightly and the K to fall. About one-half of the dogs did not show hemoconcentration or loss of extracellular fluids, when in profound shock. Three animals exhibited moderate concentration of the blood in the terminal stages, but in no case was disturbance of fluid or electrolyte balance adequate to account for the vascular collapse. Hypertonic saline (20 cc. of a 20% solution intravenously) also restored the arterial pressure of these animals to normal but the effect was temporary compared to the lasting effect of hormone. We do not know the locus of action of cortical hormone upon blood pressure. However, it may not necessarily be through the mediation of the nerve endings but may be directly upon the musculature of the vascular system. This point is now under investigation. Overdosage effects, either in intact or adrenalectomized dogs, have not been observed despite use of massive doses of hormone. Hoskins and Fierman have described a prolonged pressor effect following oral administration of glycerine extracts of adrenal cortex to human patients. Recent work on experimental hypertension indicates that the cortical hormone is concerned with blood pressure., The observation that cortical hormone has a direct effect upon blood pressure of adrenalectomized dogs which is separable and distinct from its functional control of the internal fluid and electrolyte balance of the body, in no way invalidates the earlier conclusions based upon the hormone's “salt-water” action, as offering a rational explanation of many of the phenomena occurring in adrenal insufficiency. The 2 effects of the hormone when considered together, adequately explain the circulatory collapse of adrenal insufficiency.