Interest in adrenal medullary function has been revived in recent years by the demonstration that the adrenal medulla produces two hormones, epinephrine and nor-epinephrine. Nor-epinephrine, which is also produced by adrenergic nerves (1), differs in its chemical structure from epinephrine by the absence of an N-methyl group, and is the probable precursor of epinephrine. The observation by Goldenberg, Faber, Alston, and Chargaff (2) that adrenal medullary extract from cattle (natural epinephrine, U.S.P.) contained up to 18 per cent nor-epinephrine was confirmed by Tullar (3) and Auerbach and Angell (4). Subsequently, nor-epinephrine was found in varying proportions in the adrenal medullary extracts of several mammalian species, including man, and it has been shown that the majority of pheochromocytomas contain larger amounts of nor-epinephrine than of epinephrine (5).Although the cardiovascular effects of these hormones in man have been well established (6), there are few studies concerning their comparative metabolic effects. It is highly probable that in many of the early studies of the circulatory and metabolic effects of epinephrine, mixtures which contained varying proportions of nor-epinephrine were used, since it was demonstrated in 1948 that adrenal medullary extract from cattle produced a rise in blood sugar in the rabbit comparable to that obtained with a mixture of 75 per cent epinephrine and 25 per cent nor-epinephrine, rather than that obtained with pure epinephrine (7).The similarity of the responses which occur during insulin hypoglycemia to those produced 'The work described in this paper was aided in part by grants from the Life Insurance Medical Research Fund and the Georgia Heart Association. by the administration of epinephrine, and the presence of increased amounts of epinephrine in the blood and urine during hypoglycemia (8, 9), have led to the general belief that increased adrenal medullary secretion during insulin hypoglycemia is in part responsible for the symptoms produced and for spontaneous recovery of the blood glucose level. This is further suggested by the observation in rats that a rise in blood lactic acid, similar to that which results from the administration of epinephrine, also occurs during insulin hypoglycemia. The lactic acidemia induced by hypoglycemia can be prevented by adrenal medullectomy (10).This study was undertaken 1) to evaluate certain metabolic and circulatory effects of pure epinephrine and nor-epinephrine in man and to compare these effects with those induced by insulin hypoglycemia, and 2) to determine the effect of an autonomic blocking agent on certain circulatory and metabolic changes which occur during insulin hypoglycemia in order to throw light on the mechanisms involved in these changes.
MATERIAL AND METHODSAll subjects were free of metabolic or cardiovascular disease and fasted for at least 12 hours without physical activity or sedation. Throughout the study, blood pressure was measured at one-minute intervals by the auscultatory method. Pulse rate wa...