Effect of Intravenous Epinephrine on Blood ACTH Concentration as Measured by Steroidogenesis in the Hypophysectomized Rat

Epinephrine hydrochloride, 0.5 /ig/kg, was infused into 6 normal male subjects over a 1-min period. Blood was drawn before and 2^ min after the beginning of the infusion. Blood ACTH levels, as determined by steroidogenesis in hypophysectomized rats, were unchanged by the infusion of epinephrine. These results are at variance with those of Vernikos-Danellis and Marks, who reported, in similar experiments, elevated blood levels, as determined by adrenal ascorbic acid-depletion in cortisol-blocked rats. (Endocrinology 74: 807, 1964) TfERNIKOS-DANELLIS and Marks (1) • recently reported finding increased blood ACTH levels (as measured by adrenal ascorbic acid-depletion in the cortisol-blocked rat) 2 J min after the intravenous administration of epinephrine to normal human subjects. They proposed the measurement of blood corticotropin levels following epinephrine stress as a test of the secretory functional capacity of the adenohypophysis. Because such a test appeared very promising, their studies were repeated using the adrenal secretion rate of corticosterone in the hypophysectomized rat (2, 3) as the assay procedure. By this assay technique, no effect of epinephrine on blood ACTH levels was demonstrated. Materials and Methods Six normal male subjects, ranging in age from 21 to 38 years, were studied. All subjects were fully aware of the aims of the study and of the physiological effects to be expected from the administration of epinephrine. All studies were performed between 1:00 and 3:00 PM after a 15min recumbent rest period. Epinephrine hydrochloride, 0.5 Mg/kg in 10 ml of normal saline, was infused intravenously over a 1-min period by means of a Harvard infusion pump. All subjects noted palpitations and tremor within 30 sec of the beginning of the infusion and a feeling of warmth following the infusion. An increased Received November 13, 1963. This investigation was supported by USPHS Research Grants AM-5581-02 and AM-06-99101, from the National Institute of Arthritis and Metabolic Disease. 1 Fellow of the United Health Foundation of Western New York. pulse rate, tremor, pallor and tachypnea during the infusion, and flushing after the infusion, were observed in all subjects. Fifty ml blood samples were collected into heparinized syringes prior to and 2? min after initiation of the infusion. Fifteen ml aliquots of each sample were saved for immediate injection into assay animals, and plasma was separated from the remainder of each sample and frozen for future testing. Assays for corticotropic activity were performed on female rats of the Holtzman strain weighing approximately 200 g. The rats were hypophysectomized from 2 to 4 hr prior to use as assay animals. Assays were carried out as reported previously (2, 3): (a) 5 ml of whole blood was injected into the femoral vein; (b) 5 min later the left adrenal vein was cannulated and adrenal venous blood was collected for 4 min; (c) the corticosterone concentration of adrenal venous plasma was determined by the method of Guillemin et al. (4) and the adrenal secretion rate of corticosterone was computed. Results were expressed as m^g of corticosterone secreted per min. Since 3 persons were performing the assays simultaneously, all injections were completed within 20 min after the blood was drawn. Five ml aliquots of plasma were injected into assay animals the following day and assays were carried out as described above. Results and Discussion The results are summarized in Table 1. No difference of adrenal secretion rate was noted between animals injected with 5 ml of normal saline and 5 ml of blood obtained from normal male subjects before (t =0.763, p>0.5) or 2\ min after (t = 1.205, p >0.2) infusion of epinephrine, 0.5 Mg/kg, or between animals injected with 5 ml of blood obtained before and after infusion of epinephrine (t =0.678, p >0.5). Since the response