Comparison of Inulin and Creatinine Clearance in the Normal Dog

Self Cite

329

The mechanism by which pituitary antidiuretic hormone (ADH) produces its renal effect has not been clearly established. Under ordinary conditions, in the absence of ADH, urine of a concentration considerably below that of plasma is produced in large volume. With increasing amounts of ADH, administered or secreted, the osmotic pressure of the urine rises to and above that of plasma. With respect to total water balance, the quantitatively more important contribution to water economy is the change between maximally dilute and isotonic urine, since this, in normal man, may involve a change in water excretion in excess of 10 ml. per minute. The further saving of water effected by the elaboration of hypertonic urine is a relatively small one, amounting, at usual rates of solute excretion, to not more than an additional 1 or 2 ml. per minute. Thus, although it is commonly stated that the function of ADH is to cause the excretion of a hypertonic urine, its more important function might be better defined as preventing the excretion of a dilute urine.Recent studies of the effects of posterior pituitary extracts on frog skin have shown that these preparations markedly reduce the resistance of this membrane to the flow of water in response to gradients of osmotic pressure (1). Observations on frog bladder also suggest this mechanism of action (2). It would seem reasonable to examine the extent to which a similar mechanism of action could explain the effects of ADH on the concentration of the urine. Since the change from dilute to isotonic urine is clearly in the direction of the dissipation of an osmotic gradient, this effect of ADH could well be attributed to a change in the 1 The material in this paper was presented in summary form at the meeting of the American Society for Clinical Investigation, Atlantic City, May, 1956. 2Dr. Davidson's work was done under the tenure of an American Heart Association Fellowship. permeability of the tubule membrane to water. The change to hypertonicity cannot be so readily attributed to an effect on water permeability without some assumptions as to the mechanism by which the hypertonicity is produced. However, it is a reasonable hypothesis that the mechanism for the production of hypertonicity is not dependent upon ADH but that its effects are unmasked, in the presence of ADH, by 1) changes in the volume and concentration of urine delivered to it and, possibly, 2) changes in the permeability of the membranes separating the concentrating mechanism from the urine in the tubule lumen.The most tenable view of the mechanism by which the urine is diluted is that the process involves abstraction of solute in a segment of the tubule, -presumably the distal convoluted tubule, relatively impermeable to water (3); indeed, the results to be presented strongly support this assumption. The only solute available in quantities adequate to account for the volume of water freed of solute in the process of urine dilution is sodium and its equivalent anions. Anything which limits the amount of sodium salts...

Section: Resultscontrasting

confidence: 58%

Production of Hypertonic Urine in the Absence of Pituitary Antidiuretic Hormone1

Berliner¹,

Davidson²

1957

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329

“…Creatinine was determined by the method of Kennedy, Hilton, and Berliner (5) and inulin by the method of Walser, Davidson, and Orloff (6). Urine and plasma osmolality were determined cryoscopically using the instrument developed by Bowman, Trantham, and Caulfield (7).…”

Section: Methodsmentioning

confidence: 99%

“…It should be noted that urine remained hypotonic to plasma during the administration of either 0. 5 rates of vasopressin administration over the range of solute excretion examined in these studies. 8 The transition in urine concentration from hypertonic to hypotonic observed when 1.5 to 4.0 mU per Kg.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Variations in Solute Excretion and Vasopressin Dosage on the Excretion on Water in the Dog

Orloff¹,

Wagner²,

Davidson³

1958

It has been known for some time that osmotic diuretics may modify the effect of vasopressin on urine concentration (1, 2). However, it has been generally assumed that urine will remain hypertonic to plasma if sufficient hormone is administered irrespective of the extent of the solute diuresis. This conclusion was based on the thesis that the major action of vasopressin is to promote the elaboration of a hypertonic urine presumably by a process involving active water reabsorption. Smith (3) and Wesson and Anslow (4), on the other hand, have suggested that vasopressin increases permeability of the tubule membrane to water in the distal segment, permitting osmotic equilibration in this area, and thereby diminishing the volume of isosmotic fluid delivered to a hypothetical concentrating site in the collecting duct.The experiments to be reported were designed to reexamine in a quantitative fashion the effect of solute excretion on the renal response to purified arginine vasopressin. The data have been interpreted in the light of present information concerning the probable mode and sites of action of the hormone. METHODS AND MATERIALExperiments were performed on trained, unanesthetized female dogs weighing approximately 20 Kg. each. Preliminary studies were performed on animals which had undergone section of the supraoptico-hypophyseal tracts and pituitary stalk. Despite persistent polyuria and polydipsia it was impossible to rule out the presence of residual antidiuretic hormone in these animals. The infusion of hypertonic saline during water diuresis resulted in a gradual decrease in free water clearance (CH20, see below), albeit at a lesser rate than in normal dogs; and further, early morning urine was invariably hypertonic to plasma. Consequently it was concluded that these preparations afforded no significant advantage over normal dogs for the purpose of these studies.All experiments were performed following a 12 to 16 hour fast. Water was allowed ad lib. when necessary. Dogs were loosely restrained and maintained in the supine position throughout the experimental procedure. Extraneous stimuli were reduced to a minimum to insure adequate suppression of antidiuretic hormone release in hydrated animals. Bladder urine was collected by means of a soft indwelling rubber catheter. At the beginning of each study the dogs were given a quantity of water by stomach tube equal to 3 per cent of their body weight. Thereafter this positive water balance was maintained by administering 2.5 per cent glucose in water intravenously at a rate sufficient to maintain plasma osmolality relatively constant. Solute diuresis was produced by intravenous administration of an isotoni'c solution of mannitol into the opposite limb.The clearance of inulin or crtatinine was used as a measure of glomerular filtration rate. Creatinine was determined by the method of Kennedy, Hilton, and Berliner (5) and inulin by the method of Walser, Davidson, and Orloff (6). Urine and plasma osmolality were determined cryoscopically using the instrument develop...

“…As the operative procedure was begun, the animal was given intravenously within a 5 to 24-minute period 400 Creatinine was determined in diluted urine and protein free filtrates of plasma by the method of Kennedy, Hilton, and Berliner (5). Total CO2 in plasma and urine was determined by the manometric extraction technique of Van Slyke and Neill (6).…”

Section: Methodsmentioning

confidence: 99%

The Effect of Acute Elevation of the Plasma Chloride Concentration on the Renal Excretion of Bicarbonate During Acute Respiratory Acidosis 1

Hilton¹,

Capeci²,

Kiss³

et al. 1956

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It has been postulated recently that renal bicarbonate reabsorption is entirely dependent on the exchange of hydrogen ions, derived from the dissociation of carbonic acid within the cells of the renal tubule, for the fixed base of filtered bicarbonate in the tubular urine (1-3). According to this theory, an elevation of the CO2 tension of the extracellular fluid results in an increase in the rate of bicarbonate reabsorption because it leads to an increase in the rate of hydrogen ion secretion.Earlier studies, however, indicate that chloride reabsorption may interfere with bicarbonate reabsorption presumably because of competition between these two ions for some common transport mechanism in the proximal tubule (4). Since plasma pCO2 was apparently within normal range in those experiments, it was thought of interest to study the effect of hyperchloremia on bicarbonate reabsorption in the presence of an elevated extracellular pCO2.Our results indicate that under these circumstances the rate of bicarbonate reabsorption does not depend entirely on the CO2 tension, but may, in part, depend upon the rate of chloride ion reabsorption. METHODSNormal adult mongrel female dogs were anesthetized by the intravenous administration of 0.46 to 0.62 mg. of sodium pentobarbital per kilogram of body weight. The trachea was cannulated with a "Y"-shaped glass tube, the two free arms of which served as inspiratory and expiratory airways by means of flutter valves. The animals breathed spontaneously throughout the entire experiment. The abdomen was opened by a midline in-1 Supported by grants-in-aid from the New York Heart Association and the American Heart Association.2Fellow of the New York Heart Association.3 Frances H. Zabriskie Fellow, St. Luke's Hospital.cision and each ureter cannulated with a polyethylene tube. The abdomen was then closed by a continuous silk suture and the polyethylene tubes brought through the suture line, care being taken not to kink the ureters and tubes. Urine was collected directly under mineral oil contained in a graduated cylinder.During the successive periods of study, the dog breathed first room air, then a mixture of CO, and air containing 10 per cent of CO,,The different solutions were administered at desired rates by means of a constant-speed Bowman pump via a cannulated brachial vein. As the operative procedure was begun, the animal was given intravenously within a 5 to 24-minute period 400 ml. of a 0.15 molar sodium bicarbonate solution containing 0.375 Gram per cent of creatinine. Then a sustaining infusion containing from 0.93 Gram per cent of NaHCO, to 1.175 Gram per cent of NaHCO, (0.11 to 0.14 molar solution) was administered at rates varying between 6.4 and 18.5 ml. per minute. This infusion also contained an amount of creatinine such that the dog received 15 mgm. of creatinine per minute. When the operative procedures were completed, a fifteen to thirty-minute equilibration period was allowed. Then control determinations were made, the animal breathing room air and receiving the sustaini...