1. A method of standardising pressor activity of pituitary extracts with an order of precision not significantly inferior to that obtained with the virgin uterus of the guinea‐pig is described. 2. For quantitative or clinical purposes involving action on the circulatory system, pituitary extracts free of depressor substances can be prepared, as SCHAFER and VINCENT indicated, by alcoholic extraction. 3. For depressor‐free extracts tolerance is a function of the dosage and time interval between successive injections. 4. With appropriate time intervals a remarkable constancy of response of the same character and order of magnitude as the initial rise in blood‐pressure may be obtained with the spinal cat for periods up to twenty hours. 5. With sub maximal doses the period of recovery for response of the same order as that obtained on initial injection is rather less than an hour. 6. Consistent discrimination tending to increase as the experiment proceeds may be obtained for ten or twelve hours between hourly doses differing by 10 per cent. 7. The curve obtained by plotting increase of pressure against dose shows the steepest gradient near a point corresponding to half the dose requisite to produce maximal response; and the best discrimination is obtained by working with a standard in the neighbourhood of this value. 8. It is therefore suggested that the match should be made against a standard for which a curve of reference is kept in use: the limit of accuracy can be defined in any instance by interpolating a known dilution between two injections of the standard.
In this communication an attempt has been made to explore the possible existence of independent components of the vasomotor activity of pituitary extracts by studying their effects in terrestrial vertebrates other than mammals. A comparison of histamine and other reagents with that of commercial pituitary preparations and laboratory pituitary products free from the substances producing a depressor response in the mammal has been made in the bird (duck and fowl), reptile (tortoise), and amphibian (frog). Pituitary extracts do not produce perceptible effects on the blood‐pressure of the reptile and amphibian, when administered in quantities which are of an order of magnitude to which physiological significance could be justifiably attached. Whereas adrenaline produces a rise in arterial blood‐pressure in all four classes of air breathing vertebrates, pituitary extracts which had no depressor action in the mammal consistently evoke depression in bird and reptile : and there seems to be a strong presumption in favour of the conclusion that the pronounced depressor action of small doses of pituitary extract on the a vine circulation is not due to the substance or substances responsible for the lowering of blood‐pressure in the mammal. It has been necessary to reinvestigate the depressor response in the mammal, and the results obtained demonstrate the part played by initial pressure in determining the character of the response to successive doses of pituitary extract and to histamine. Emphasis is laid on the misleading nature of comparisons indiscriminately based on testing with etherised and decerebrate animals in previous biochemical investigation into the nature of the pressor activity of pituitary extract. The expenses of this research were defrayed in part by a grant from the Earl of Moray Fund.
[1912] were induced by its existence to turn their attention to the oxytocic activity, and they devised the method of assay with the isolated uterus of the virgin guinea-pig, and this is now probably the method most extensively employed. Hogben, Schlapp and Macdonald [1924], in elaborating their method of pressor assay on the spinal cat, were able to show that for small doses up to 2 mg. of dried posterior pituitary substance, the period of tolerance did not exceed 1 hour.Little is known concerning the factors responsible for the tolerance, but Dale and Laidlaw [1912] surmized that it might be the consequence of a slow disappearance of the active principles from the blood. On the other hand, it seemed possible that an effect on the blood volume was to some extent concerned. Underhill and Pack [1923], giving "pituitrin" intravenously to dogs, found a 20 p.c. reduction in hEemoglobin occurring both with and without the simultaneous administration of water.In the experiments to be described here, the disappearance of the active principles from the blood has been followed, its relationship to the tolerance investigated and the effect of the principles on the blood volume is examined. The excretion of the pressor principle in the urine is studied quantitatively, and the destructive action of tissue extracts on the oxytocic and pressor activities demonstrated.
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