THE ENDOCRINE ORGANS, OR DUCTLESS GLANDS 777 



excitatory, a less marked inhibitory influence may be simultaneously 

 developed. The inhibitory effect may also sometimes be evoked by 

 doses of epinephrine very much smaller than those used to produce 

 excitatory effects. These facts are well illustrated in the case of the 

 muscle fiber of the blood vessels. With an ordinary dose of epinephrine 

 constriction occurs; after ergotoxin the same dose of epinephrine causes 

 dilatation. Or this latter result may also be obtained by administer- 

 ing to a normal animal quantities of epinephrine that are very much 

 smaller than the usual quantity. The coexistence of inhibitory and ex- 

 citatory influence is also well noted in the case of the uterus. In some 

 animals the effect of epinephrine on this organ is to augment its rhythmic 

 contractions, in others to inhibit them. In the former case, however, if 

 ergotoxin is first of all administered, epinephrine in its usual dosage will 

 invariably produce an inhibitory effect. The ergotoxin no doubt acts on 

 the receptor substance, and similar effects have also been produced with 

 apocodeine. 



It was first noted by Moore and Purinton 14 that the usual rise of blood 

 pressure which followed the injection of epinephrine was replaced by 

 a depressor effect when the dose was very small. Later it was shown that 

 this was not an isolated instance of a reversed action of epinephrine 

 when employed in high dilutions; the intestinal tone is augmented by 

 minute doses (1 part in 500 million or more according to Hoskins) 15 and 

 the contractions of the pregnant uterus inhibited. 



The nature of the vasomotor effects differs not only in accordance with 

 the dosage, but it is of dissimilar sign in different vascular areas, though 

 the dilution of the drug be kept constant. Hartman 16 has shown that 

 epinephrine in high dilution causes dilatation of the peripheral vessels 

 simultaneously with vasoconstriction in the splanchnic area. These con- 

 clusions were drawn from blood pressure records taken in two series of 

 experiments in which the splanchnic and the peripheral vessels, respec- 

 tively, were excluded from the circulation. In the former series a fall 

 in pressure was effected, in the latter a pressor response was obtained. 

 Hoskins, Gunning and Berry 17 went further and found, by means of 

 plethysmographic records, that all the vessels of the peripheral circula- 

 tion did not respond alike to a given dose, those of the muscles being 

 dilated, while those of the skin underwent simultaneous constriction. 

 The variations in limb volume and of blood pressure would then depend 

 upon which of these effects predominated at the time. Neither are all 

 parts of the splanchnic area affected similarly, for, though the spleen 

 and kidney both show vasoconstriction with all dilutions, the intestinal 

 vessels are constricted by small doses, but dilated by large. (Hartman). 

 The vasodilator responses to epinephrine are not, as is the case with the 

 constrictor effects, mediated by the myoneural junction. The vasodilator 



