@article {STEWART205, author = {G. N. STEWART and J. M. ROGOFF and F. S. GIBSON}, title = {THE LIBERATION OF EPINEPHRIN FROM THE ADRENAL GLANDS BY STIMULATION OF THE SPLANCHNIC NERVES AND BY MASSAGE}, volume = {8}, number = {5}, pages = {205--245}, year = {1916}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {1. It is shown (on cats and dogs) that the response of the denervated eye to stimulation of the peripheral end of the splanchnic nerves, is due solely to the passage of a substance in the blood stream from the adrenals to the eyeball. For (a) When the venous path is blocked the response fails, but appears on releasing the block, and at the same interval of time as when the vessels are free. The active substance must therefore have accumulated during the period of stimulation of the nerves behind the block. (b) When the heart is stopped by stimulation of the peripheral end of the vagus, stimulation of the splanchnics produces no effect on the eye. But on allowing the heart to beat again, the eye response occurs at approximately the same time from the moment of reestablishment of the circulation, as the time interval between stimulation of the splanchnics and the response with the circulation going on normally. During the stoppage of the circulation, by complete cardiac inhibition, accordingly, stimulation of the splanchnics must have caused liberation of the active substance at the same point from which it starts when the splanchnics are stimulated without cardiac inhibition. (c) When the circulation is slowed without being stopped, as by producing partial inhibition of the heart through the vagus or by hemorrhage, the interval between the beginning of stimulation of the splanchnics and the appearance of the eye response is correspondingly increased. (d) It is possible to find a strength and duration of stimulation of the splanchnics with which no eye response will be obtained, when the ipsilateral or both carotids are clamped, but which will give a response with the vessels free. With longer or stronger stimulation, a response, but a belated one, may occur even with the carotids clamped. The abolition of the response, and its retardation, can be imitated when appropriate doses of adrenalin are injected into the femoral vein with the carotids clamped or free. (e) When adrenalin is injected into the left renal vein, or into the central end of the femoral vein, in suitable amount to produce an eye response approximately equal to that produced by a given stimulation of the splanchnics, the interval of time after which the response follows is sensibly the same for adrenalin injection as for splanchnic stimulation. 2. When the aorta is clamped, and the splanchnic then stimulated, a response may be obtained in the eye while the clamp is still on, or only after its removal, or both during the application and after removal of the clamp. There is some variability in this regard in different experiments. There is also a somewhat greater variability in the time interval at which the response appears, than in observations in which the splanchnics are stimulated with the vessels free, or with the veins clamped. The interpretation of these differences is discussed. 3. Circulation time measurements show that there is always more than sufficient time for a substance to have been carried in the blood from the adrenals to the eye before the appearance of the eye reactions. 4. The latent period of liberation of epinephrin from the adrenals on stimulation of the splanchnics is short since the time interval after which the eye response occurs is sensibly the same whether it is evoked by splanchnic stimulation or by the injection at the level of the adrenals of a quantity of adrenalin sufficient to elicit a response similar in character and amount. 5. The minimum period of stimulation of the splanchnics needed to liberate sufficient epinephrin to elicit a response in the denervated eye is very brief (a fraction of a second). With a current of given intensity the amount of the response increases up to a certain point with the duration of the stimulation. 6. Massage of one or both adrenals causes definite eye response in an animal in which stimulation of the splanchnics has been causing it, and at the same interval of time. When, after repeated excitations of a splanchnic nerve, the reaction on the eye ceases to be obtained, it can still in general be elicited by mas sage of the corresponding adrenal. But this reaction is soon exhausted. 7. Good eye reactions have been obtained by stimulation of the splanchnics in cats, in which attempts were made before the experiment to exhaust the epinephrin store of the adrenals, for example, by frightening or by administration of morphin. It did not seem that it was easier to exhaust the capacity of the splanchnic nerves for eliciting these reactions in such animals, than in animals which were guarded as much as possible against preliminary exhaustion of the epinephrin store by psychical disturbances.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/8/5/205}, eprint = {https://jpet.aspetjournals.org/content/8/5/205.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }