276 SCIENCE PROGRESS 



but it will be seen that, so far, satisfactory experimental evi- 

 dence of an independent activity on the part of the capillaries 

 is wanting. This was not afforded until the experiments of 

 Dale and Richards in 191 8. Dale and Laidlaw in 1910 were 

 struck by the puzzling action on the blood-pressure of a base, 

 histamine, obtained by removal of carbon dioxide from the 

 amino-acid, histidine, a constituent of most proteins. In the 

 dog, cat, and monkey, a marked fall of blood-pressure is pro- 

 duced by very small doses. Now, in the case of certain other 

 drugs having this effect, depression of the heart being ex- 

 cluded, it was known that dilatation of the arterioles was 

 produced, and the explanation of the fall of blood-pressure 

 was easily explained by decrease of peripheral resistance. 

 But tests of the action of histamine on various kinds of smooth 

 muscle, including that of the arteries, showed that it caused 

 contraction, and therefore narrowing of the arterioles, an effect 

 which by itself alone would produce rise of blood-pressure. 

 By a number of ingenious experiments, the details of which 

 cannot be given here, Dale and Richards showed that his- 

 tamine causes a widespread dilatation of the capillaries, inde- 

 pendent of its effect on the arterioles, which are constricted. 

 It is evident, therefore, that the capillary effect is great enough 

 to overpower that of the arterioles. How is the fall of blood- 

 pressure produced ? It seems improbable that a dilatation in 

 such a wide bed as the capillary district, even in normal con- 

 ditions, should have any marked effect in decreasing the peri- 

 pheral resistance, especially when the arterial constriction has 

 reduced the blood flow to a low degree of magnitude. The 

 result must be due to removal of blood from actual circulation, 

 an interpretation confirmed by the examination of the heart, 

 which is seen to be empty of blood. In fact, the blood, soaked 

 up by the capillaries as by a sponge, takes no more part in the 

 general supply of the organs with fresh oxygenated blood than 

 if lost by haemorrhage. In this work, the fall of blood-pres- 

 sure caused by very small doses of adrenaline in certain 

 conditions was shown to be due to its dilator action on the 

 capillaries. 



The practical interest of these experiments lies in the fact 

 that histamine is one representative of a group of substances 

 obtained by disintegration of the protein molecule. In the 

 state of " shock " brought on by extensive injury to tissues, 



