198 E. G. HOSKmS 



duced to negligible proportions. The experiments were carried out on 

 7 dogs under chloroform anesthesia. The vagi were paralyzed by means of 

 atropin. Carotid blood-pressure was recorded. From ten to twenty in- 

 jections were made in each animal. It was found that the intravenous 

 injection of extract of the medullary portion of the glands in doses equiva- 

 lent to 0.005-0.010 mg. of the gland substance per kilogram body-weight 

 gave pure rises of pressure of from 20 to 40 millimeters. With doses 

 of 0.001 to 0.003 mg., a brief rise followed by a well-marked fall of pres- 

 sure was seen. In still smaller doses only depressor effects were obtained. 

 Such depressor effects were not elicited, however, in all cases ; two of the 

 seven animals gave only pressor responses. These investigators left open 

 the question whether the reversal of reaction was due to the presence 

 of some unrecognized "impurity" better able than the true "active prin- 

 ciple" to maintain its potency in high dilution or to the stimulation of 

 some true depressor mechanism. 



The fact that suprarenal extracts are able to produce vasodilatation and 

 thus fall of blood-pressure was reported by Dale (1906). In the course 

 of a study of the pharmacology of ergot he made the interesting dis- 

 covery that ergotoxin or chrysotoxin has the peculiar property of para- 

 lyzing all of those sympathetic fibers which have a stimulating function, 

 leaving more or less, intact those which have an inhibitory function. A 

 dose of epinephrin, which in a normal animal would evoke a marked 

 rise of blood pressure, was found, after poisoning with ergotoxin, to 

 bring about a marked fall of pressure. This work was generally accepted 

 as proving that epinephrin can cause vasodilatation. 



Somewhat before this time, however, it had been shown by S. J. 

 and Clara Meltzer (1903) that subcutaneous injection of suprarenal ex- 

 tract in the rabbit can lead to well-marked and persistent dilatation of 

 the blood-vessels of the denervated ear. 



Elliott, in his classical paper in 1905, reported that he had in some 

 cases observed very dilute solutions of epinephrin to cause lowering of 

 the blood-pressure in the cat, but apparently he was unwilling to accept 

 the observations as valid because he found that solutions of 1 : 600,000 or 

 1 :200,000, if "slowly and exactly made," produce only rise of pressure. 

 "Straightforward experiments failed to prove vascular dilatation by 

 adrenalin." In 1912, however, the same investigator noted that in some 

 cases, when the splanchnic nerves were stimulated, a drop in blood-pres- 

 sure occurred, which coincided with signs of epinephrin discharge (dilata- 

 tion of the pupil). He also noted that after extirpation of the suprarenals 

 this depresor effect could be simulated by injecting epinephrin during 

 splanchnic stimulation. 



Despite such observations as the foregoing, so firmly established was 

 the idea that epinephrin is a pressor drug that its vasodilator properties 

 were for years deemed negligible. In connection with other investiga- 



