This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
tion of the renal vessels, succeeded by dilatation, or vice versa. Thus Mr. Power and I found that on injecting digitalis into the circulation of a dog, the blood-pressure rose, but the secretion of urine was either greatly diminished or ceased altogether. Here it is evident that the renal vessels had contracted so much as to prevent the circulation through the kidney, notwithstanding the rise which had taken place in the blood-pressure. After a while the blood-pressure began to fall, and then the secretion of urine rose much above its normal, showing that the general blood-pressure was then able again to drive the blood into the kidneys.1 fig. 151. - Curves showing the effect of erythrophloeum upon the blood-pressure and secretion of urine. From Phil. Trans., vol. clxvii.
Similar observations were made by Mr. Pye and myself with regard to erythrophlceum; and the accompanying curves (Fig. 151) show well the result upon the urine of the mutual action of the rise in blood-pressure and the contraction of the renal arteries upon the secretion of urine. It will be noticed that at first the blood-pressure rises more quickly than the secretion of urine, the circulation through the kidney appearing to be opposed by the renal arteries. This opposition is then overcome, and the secretion of the urine rises more quickly than the general blood-pressure. The renal vessels again appear to contract, so that the urine diminishes while the blood-pressure rises still further. We have then oscillations due first to one factor and then to the other being predominant; and then, when the blood-pressure rises to its maximum, we find that the urine is at its minimum, the secretion of urine again rising as the blood-pressure falls.
A good deal of discussion has arisen regarding the mode of action of digitalis, and it has been stated by many to act as a diuretic only in cases of heart disease, and to have no diuretic action in health. In my own experiments, however, I found that it acted as a very marked diureticeven in health, and the explanation of this discrepancy may possibly be that in my own case the blood-pressure was low, whereas in the others it was probably much higher; but I am uncertain regarding the true explanation, though I am certain of the fact.
1 Royal Society's Proceedings, No. 153, 1874.
By causing increased secretion of water through the kidneys diuretics may increase the concentration of the blood and thus produce thirst, or cause absorption of water from the intercellular tissue or serous cavities in dropsies. In my own experiments on digitalis I weighed all my food and measured all my drink for nearly six months, taking exactly the same quantity every day. After producing profuse diuresis by a large dose of digitaline (sixty milligrammes in two days), such thirst ensued that I was forced to take a quantity of water to allay it.1
Mode of Action of Diuretics. - From what has already been said, it is evident that diuretics may act in several ways. They may act:
A, on the circulation in the kidney, raising the pressure in the glomeruli - (1) locally, (a) by contracting the efferent vessels, or the arterial twigs which pass directly to the capillary plexus; (b) by causing dilatation of the renal arteries, and thus increasing the supply of blood to the kidney. This they may do also in more ways than one, for they may either paralyse the vaso-motor nerves of the kidney, or act on vaso-dilating mechanisms. (2) they may raise the blood-pressure generally by causing the contraction of vessels in other parts of the body.
Fig. 152. - Diagram to show the parts of the secreting apparatus of the kidney which are probably affected by different diuretics.
B. Other diuretics may act on the secreting- cells of the tubules, and may increase both the amount of water and the amount of solids excreted by them.
1 The experiments were made in 1855, and published in part in my thesis on Digitalis, with some Observations on Urine. London : Churchill & Co., 1868.
2 Munk, Central, f. d. med. Wiss., No. 27, 1886.
Diuretics have already been classified as stimulating and sedative; and the sedative class agrees very closely with the one which we have just indicated as acting on the kidney through the circulation.
From what has been said of the action of diuretics it is evident that we may hope to do much more by combining them than by using them singly. Thus we see that digitalis instead of acting as a diuretic may completely arrest the renal circulation and stop the secretion altogether. If, however, we can combine it with something which will produce dilatation of the renal vessels, while the general blood-pressure remains high, we shall greatly increase the circulation through the kidney, and obtain the desired result. Experiments in regard to this were made by Grutzner with nitrite of sodium. He found that this substance increased the secretion of urine when the blood-pressure was reduced to a minimum by curare; and he found that it also had this effect when the blood-pressure was raised by imperfect respiration. When the vaso-motor centre was greatly stimulated, however, by allowing the blood to become very venous, the nitrite of sodium no longer produced any increase of secretion.
Caffeine, again, has an action on the kidney similar to that of physostigmine on the salivary glands (p. 358). Thus, by affecting the vaso-motor centre, it not only produces contraction of the vessels generally, including those of the kidney,3 but stimulates the secreting cells.4 The contraction of the vessels may counteract this stimulating action, so that no urine is secreted as in the case of digitalis (p. 430), but when the renal nerves are divided a copious secretion of urine takes place.