THE CIRCULATION OF THE BLOOD 699 



The usual effect of strychnine in converting inhibition into excitation is shown 

 in Fig. 247 to apply to the vasomotor centres. In this figure, the effect of 

 gradually increasing doses in converting the depressor fall into a rise is seen. In 

 the further analysis of the action of this drug I met with inexplicable results, 

 until I realised that it must convert, not only the inhibition of the constrictors 

 into an excitation in depressor reflexes, but also that of the dilator centre in 

 pressor reflexes. Thus the vaso-dilators may be excited in a pressor reflex after 

 strychnine, and one obtains conversion of constriction by inhibition of dilator 

 tone into dilatation by excitation of the dilator centre, as shown in Figs. 248 

 and 249. 



The opposite effect of chloroform is well shown in Mathison's curve (Fig. 128, 

 page 428, and in Fig. 129). 



The question of the nature of the automatic tone in the vasomotor centres has 

 been touched upon above (page 546). 



It is well known that a considerable rise of arterial pressure occurs in asphyxia, 

 and we have referred to Mathison's results on the action of asphyxial products in 

 an earlier page (page 632). The experiments of Sollmann and Pitcher (1911) 

 may be added. They find that the asphyxial stimulation of the bulbar vaso- 

 motor centre is due to carbon dioxide, and is absent if accumulation of this acid 

 is prevented, although oxygen is absent. We may regard it as possible that the 

 normal stimulation of the centre is brought about by the carbon dioxide tension 

 of the blood, like that of the respiratory centre. 



Chemical Regulation of the Blood Flow. The appropriate sensibility of the 

 blood vessels to the products of the activity of cells, by which an automatic vaso- 

 dilatation is caused, has been referred to in speaking of the coronary circulation 

 (page 680). The importance of the action of metabolites in this respect was first 

 clearly realised by Gaskell (1880, pp. 66-70). As acid products, and especially 

 carbon dioxide, are the usual results of cell metabolism, it is natural to look for 

 direct evidence of the effect of increase of hydrogen ion concentration. Gaskell 

 showed that lactic acid produces decrease of tone, and I showed later (1901, 1) 

 that carbon dioxide has the same effect. The work of Hooker (1911-1912) con- 

 firmed these results, and was extended to the action of other substances. It 

 should also be mentioned that Severini (1876-1881) had already described dilata- 

 tion of capillaries by carbon dioxide and constriction by oxygen. The fixed acid 

 products come chiefly into play in deficiency of oxygen supply, as in asphyxia, or 

 when oxygen is consumed at a rapid rate in great activity of the cells. Hooker 

 showed that oxygen and also calcium ions increase vascular tone, and that carbon 

 dioxide, 'urea, sodium, and potassium ions decrease it. Schwarz and Lemberger 

 (1911) found that the injection of 1 cub. cm. of O'OOl molar hydrochloric acid 

 into the central end of the left subclavian artery caused obvious dilatation of the 

 vessels of the submaxillary gland, although, of course, only a part of the acid 

 reached the gland. Comparing the action of different acids, their action was not 

 found to correspond to the H ion concentration. But, as the authors point out, 

 and as we have seen above (page 200), the effect is really produced by carbon 

 dioxide driven off from the bicarbonates of the blood, which would naturally be 

 proportional to the total molar amount of the acid introduced. Acids weaker 

 than carbon dioxide, such as glycine and alanine, were inactive. 



This local effect, it will be noticed, is opposite to that on the centres, on which, 

 as we have seen above, carbon dioxide has an exciting influence, and Mathison 

 showed (1911) that the direct action of potassium salts on the centres is also 

 excitatory. 



There is often present, in extracts of tissues, especially when prepared by 

 boiling, some substance or substances which have a powerful dilator effect on 

 blood vessels. This is the case with acid extracts of the mucous membrane of the 

 small intestine. Now Barger and Dale (1911) have shown that such boiled acid 

 extracts contain the salt of a base, which is also obtained by the splitting off of 

 carbon dioxide from histidine, and is /3-iminazolyl-ethylamine. This compound is 

 present in the cells when scraped off, since it can be extracted by alcohol (Bayliss 

 and Starling, 1902, 1, p. 335), but whether it is actually present in the living 



