2NTRA VENOUS INJECTION OF SUPRARENAL EXTRACT. 955 



a plethysmograph or oncometer, the instrument indicates a great 

 diminution in volume of the organ, which can only be accounted for by a 

 contraction of its arterioles. 1 This contraction is produced by the direct 

 action of the drug upon the muscular tissue of the smaller arteries, and 

 not indirectly through the vasomotor centre ; for it obtains in the mammal 

 equally well with the spinal cord cut or the bulb destroyed (Fig. 90), or 

 even in the case of the arm after the brachial plexus has been severed 

 (Fig. 91). In the frog it is produced also with the brain and spinal cord 

 completely destroyed, when salt solution containing suprarenal extract is 

 allowed to flow through the arteries. Under these circumstances the 

 flow of fluid, which, without the suprarenal extract, may have been com- 

 paratively rapid, becomes almost completely stopped, and this can only 

 be due to the direct action of the extractive substance upon the muscular 

 tissue of the smaller arteries. 



The enormous rise of blood pressure which is got after the vagi have 

 been cut, is shown in the tracings (Figs. 89 and 90) : the pressure may rise 

 to four or five times its original height. Hardly any other agent will 

 produce such an enormous increase of pressure, except direct stimulation 

 of the vasomotor centre. It is not the case, however, that the elevation 

 of blood pressure, and the contraction of the arteries, is due to the 

 stimulation of the vasomotor centre by the drug, as was supposed by 

 Cybulski and Szymonowicz, for, as we have seen, the action is essentially 

 a peripheral one. As shown by Oliver, 2 it will occur if the extract be 

 directly applied to the vessels of the mesentery, either during life or 

 in the " surviving " condition. 



The effect of intravenous injection upon the blood pressure passes off in the 

 course of a few minutes. After a dose, no matter whether small or large, has 

 been injected into a vein, and has produced the results which we have 

 recorded, the blood vessels slowly resume their ordinary calibre, the augmenta- 

 tion and increased frequency of the heart's beats become gradually lessened, 

 and the blood pressure recovers its normal condition. Whilst the pressure is 

 raised under the action of suprarenal extract, there is apparently no possibility 

 of inhibiting the arterial contraction ; even the strongest stimulation of the 

 depressor nerve, which under ordinary circumstances produces through the 

 vasomotor centre a marked dilatation of the arterioles, is without result during 

 the activity of this extract. The question naturally arises, How is it that the 

 effect so soon disappears ? In what manner is the active principle eliminated ? 

 It is not eliminated by the kidneys, for the effect passes oft' just as quickly 

 even although the renal arteries are clamped. It is not eliminated by the 

 suprarenals themselves, for the same fact holds good for the suprarenals. It 

 passes off almost equally quickly if the aorta and vena cava are tied in the 

 upper part of the abdomen, so that there is no circulation of blood whatever in 

 the abdominal organs. It is not oxidised or otherwise destroyed by the blood, 

 for it retains its full potency even after it has been twenty-four hours in 

 contact with that fluid. The most probable explanation of the disappearance 

 of the effect seems to be that the active principle becomes packed away, and 

 eventually rendered innocuous in certain organs. That the muscles take most 

 part in this storage is probable, from the fact that the physiological effects upon 

 the skeletal muscles are manifested for a long time after the effects upon the 

 heart and arteries have disappeared. 



1 In man the effect of taking suprarenal extract 1>y the mouth is to produce a general 

 diminution in calibre of the arteries as measured by "the arteriometer (Oliver, "Ooonian 

 Lectures," Lancet, London, 1896). 



2 "Proc. Physiol. Soc. , " Journ. Physiol., Cambridge ami London, March 1897. 



