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FIG. 4. Changes in blood glucose and plasma NEFA levels in response to epinephrine infusions. I.V. injection of propranolol is shown by the arrow.Prior to blockade, epinephrine had little effect on arterial blood presure, but increased the cardiac output. Following blockade the arterial pressure was greatly increased and the heart rate and cardiac output decreased. This is explained by the fact that epinephrine is an agonist of both alpha and beta receptors. When the latter are blocked, activity at the former predominates, resulting in intense peripheral vasoconstriction, hypertension and slowing of the heart. That the slowing was reflexly induced was clear from the fact that it did not occur in atropinized dogs.Release of NEFA from adipose tissue stores is to a large extent under the control of the sympathetic nervous system. Infusions of epinephrine (9) and norepinephrine ( 10) cause temporary increases in plasma NEFA levels. Most authors( 1 1 , 1 2 ) found that pronethalol prevented the catecholamine-induced increase from occurring. However, Riggilo and Kyam( 13) reported that, although pronethalol blocked the hyperglycemic effect of catecholamines in dogs, it failed to inhibit the increase in NEFA levels. In our studies, propranolol consistently and completely blocked the release of NEFA by epinephrine even when its hyperglycemic effect was not completely abolished.

period of 2-2vi minutes to account for the plasma clearance curves of Fig. 2 solely on the basis of redistribution. This rapid rate of clearance, even after the inhibition of amine-metabolizing enzymes. is compatible with the observation that circulating catecholamines are taken up quickly by many tissues of the body(3,6).S U~V Z Q~~. The simultaneous inhibition of catechol-0-methyl transferase and monoamine oxidase (by pyrogallol and JB-835) produced only moderate prolongation of the cardiovascular effects of injected I-norepinephrine in anesthetized dogs. This prolongation of pharmacological action in presence of enzyme inhibitors was correlated with a delayed disappearance of injected norepinephrine f roni the circulation. While these results indicate that nietabolisni by these enzymes contrib-u tes to removal of circulating norepinephrine from the plasma in the dog, they further suggest that the physiological inactivation of circulating norepinephrine at the receptor sites does not require metabolic destruction of the amine by these enzymes.I am grateful to Dr. Leon Goldberg for advice and to Mrs. Frances DeCosta for technical assistance.