IT is a matter of common observation that the taking of alcoholic drinks is followed by an increased output of urine. In the case of beer-drinking, this is not surprising, since large volumes are usually consumed; and in the case of some other beverages, e.g. gin, a diuretic agent is present in the drink. The observed diuresis is usually attributed to a combination of these two factors, and most writers either state categorically or imply that alcohol per se has no diuretic action. In 1932, however, from a comparison of the diuretic effects of a given volume of water, with and without alcohol, on two subjects, Murray concluded that alcohol itself was exerting a diuretic action. No alcohol estimations were made, but from observations on the composition of the urine (chloride and phosphate concentrations) and on the inhibitory action of pituitary extract, it was concluded that the mechanism of alcohol diuresis was of the same nature as that of water diuresis.The diuretic action of alcohol has now been demonstrated on five other subjects, and its mode of action investigated by simultaneous analysis of alcohol concentration in the blood and urine. METHODSTo each subject the same volume of fluid was given on different occasions; it had a constant basis of cider (70 %) to render it more potable and varied only in its alcohol content. Since the experiments were often of long duration and avoidance of fatigue necessary in view of other aspects of the experiment, a light breakfast was allowed (tea or coffee, toast and butter). The dose of alcohol was always given 24-3 hr. after this, and was usually drunk in the space of 10-15 min. along with

Until recently the action of the antidiuretic hormone has been described as restoring 'water balance by promoting the reabsorption of the osmotically free water left by the distal reabsorption of Na. Under the action of the hormone this water is reabsorbed; in its absence this water is excreted' (Smith, 1956). Wirz (1956) has suggested an explanation of the mechanism of water reabsorption. He, and later Gottschalk & Mylle (1959), showed by micropuncture study in the rat that fluid in the first half of the distal tubule was hypotonic to plasma under all conditions of hydration, but that in dehydrated animals it became isotonic in the second half of the distal tubule and hypertonic in the collecting ducts. In the kidney producing a concentrated urine the tubular fluid comes into osmotic equilibrium first with the cortical tissue and later, in the collecting tubules, with the medullary tissue which is known to be increasingly hypertonic towards the papilla. According to Wirz's theory, the essential action of vasopressin is to increase the permeability to water of the distal parts of the nephron and collecting ducts. In 1958 Ginetzinsky found that the urine of several mammals contained hyaluronidase: this disappeared during water diuresis, but was present during osmotic diuresis, in the dog. In a histological study in rats Ginetzinsky observed that the cement substance between the cells of the collecting tubules reacted as hyaluronic acid when the animals were water-loaded, but as its polymerization products when they were dehydrated. He concluded that when stimulated by the antidiuretic hormone, the cells of the collecting tubules secrete hyaluronidase, which in turn depolymerizes the mucopolysaccharide complex of the basement membrane of the tubules, hence making 'the structures separating the tubule lumen from the interstitial tissue permeable to water. The hypotonic fluid in the tubules then follows the osmotic gradient and undergoes facultative reabsorption' (Ginetzinsky, 1958). This was a new approach to a process which had hitherto been difficult to envisage. It seemed, therefore, of interest to test Ginetzinsky's hypothesis by comparing the excretion of hyaluronidase and antidiuretic activity in urine under various conditions in man.

The mode of reabsorption of phosphate by the kidney of the cat differs from that in man and dog in that no maximal rate (Tm value) is attained (Eggleton & Habib, 1950). Glucose and phosphate reabsorptions appear to be interrelated in man and dog, and it seemed of interest, therefore, to see whether they are inter-related also in the cat. Little is known of the mode of reabsorption of glucose in this animal, though from the results of Gammeltoft & Kjerulf-Jensen (1943), who used a high plasma-glucose concentration in studying the mode of excretion of fructose and galactose in various species, it would seem that glucose has no Tm value. METHODSThe fifty-two cats used (2.0-4.1 kg body weight) were anaesthetized with intraperitoneal sodium pentobarbitone (40 mg/kg); the general operative technique has been already described (Eggleton & Habib, 1949), but for one improvement. Sodium oxalate was used as anticoagulant in place of the potassium salt and the cells, after centrifugation of the blood, were suspended in 0.9 % NaCI, filtered through gauze, and re-injected into the circulation. This procedure appeared to reduce the effect of blood sampling on the glomerular filtration rate (G.F.R.) which tends to fall towards the end of an experiment.The G.F.R. was measured by creatinine clearance, the creatinine being given either subcutaneously or with the constant glucose infusion. The latter was administered at a rate of 0-15 ml./min, its concentration varying from 5 to 50%, and sampling was not begun until at least 40 min after the beginning of the infusion. In some experiments the constant infusion was preceded by a priming dose and in others the infusion was stopped before the end of the experiment and sampling continued while the plasma-glucose concentration was decreasing.Creatinine was determined colorimetrically as the alkaline picrate, phosphate by the method of Fiske & Subbarow (1925) and glucose by the Folin-Wu method as modified by Lehmann & Silk (1952) in both plasma and urine. It was found experimentally that creatinine acted as a reducing agent in this method to the extent of 0-38 x glucose; glucose concentrations in plasma and urine were corrected accordingly. RESULTSOver the range of filtered load of glucose encountered, the amount reabsorbed increased steadily with increasing load and no Tm value was attained. There was, however, a wide scatter of individual values, and from the average of

Available evidence suggests that the diuresis following ingestion of ethyl alcohol is of the same nature as water diuresis mediated by the pituitary gland (Eggleton, 1942b). In an effort to establish further points of similarity or difference between the two types of diuresis, a class experiment on the effects of exercise on urinary excretion was performed identical with those previously reported (Eggleton, 1942a(Eggleton, , 1943 except for the substitution of alcohol as the diuretic in place of water or tea. The main results of the experiment confirmed those obtained when water had been used as the diuretic, but one unexpected difference suggested that alcohol per se might lead to the excretion of an acid urine. The matter has therefore been investigated in a number of subjects by observing the pH of the urine during water diuresis and during alcohol diuresis under strictly comparable conditions. METHODSThe class experiment was performed in the manner already described (Eggleton, 1942a), 40 g. alcohol in 250 c.c. solution being taken as the diuretic and exercise superimposed when the diuresis was well established. In the remaining experiments, each subject performed the two experiments (water ingestion 560 c.c., and alcohol ingestion 40 g. in 200 or 250 c.c., respectively) at the same time of day, usually on two successive days; in three cases, water was taken on the first day, and in four cases, alcohol. The same preliminary routine was followed on the two occasions: overnight fasting followed by an experiment in the morning, or an afternoon experiment following a 6 hr. fast, on each occasion a glass of water being taken 2j to 3 hr. beforehand.Immediately the urine samples had been collected and measured, the pH was determined by the simple comparator, using the indicator range phenol red, brom-thymol-blue and methyl red. Readings could be made within 0.1 unit. RESULTSI. Class experiment on the effect of exercise during alcohol diuresisThe average changes in the urine of eight subjects following a 60 sec. sprint during an alcohol diuresis are shown in Fig. 1, together with the results, reported earlier (Eggleton, 1942 a), of a similar experiment made during water diuresis. On the main points of difference observed in such experiments with

The recent failure to fid any satisfactory explanation of the increase in urine acidity resulting from ingestion of alcohol (Eggleton, 1946) suggested the necessity for an investigation into possible different types of urine acidity. In the experiments with alcohol, the usual criterion of urine acidity, namely changes in hydrogen-ion concentration, was adopted. In such a buffered solution as urine, however, it is apparent that an increase in hydrogen-ion concentration need not necessarily be due entirely to an increase in excretion of acidic ions: a reduction in the overall buffering power of the solution would enable an unchanged excretion of acidic ions to produce a shift in hydrogen-ion concentration.Hitherto, little attention has been paid to changes in the total buffering capacity of the urine under various physiological conditions, interest being centred rather on the 'titratable acidity' value. This value is obtained by titration of the sample with standard alkali to about pH 8 (phenolphthalein first pink) and represents the buffering power of the urine over the range pH 8 to the pH at which it was secreted. It is found, naturally enough, to vary directly with the hydrogen-ion concentration, i.e. the lower the pH of the urine sample, the higher its 'titratable acidity' value. It gives no indication of the total buffering capacity of any sample over the whole physiological range pH 4*8-8*0 except for those samples secreted at pH 4X8.