The Effect of Variations in Solute Excretion and Glomerular Filtration on Water Diuresis 1

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...

Section: Discussionsupporting

confidence: 87%

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

Orloff¹,

Wagner²,

Davidson³

1958

“…The findings suggest that the defective water diuresis is not due to a continued nonosmotic stimulus for ADH release but do not, however, entirely obviate that possibility (10,(13)(14)(15)(16).…”

Section: Discussionmentioning

confidence: 70%

“…Control collections were begun approximately 45 minutes after a priming dose and constant sustaining infusion of inulin had been started. Analysis of plasma and urine for sodium, potassium, inulin, creatinine, and osmolality were made by methods previously reported (1,10).…”

mentioning

confidence: 99%

Mechanisms of Impaired Water Excretion in Adrenal and Pituitary Insufficiency. Iii. The Effect of Extracellular or Plasma Volume Expansion, or Both, on the Impaired Diuresis*

Cutler¹,

Kleeman²,

Koplowitz³

et al. 1962

Self Cite

Earlier studies suggest that cortisol and related glucocorticoids correct the impaired water diuresis of primary and secondary adrenal insufficiency by a direct effect upon the diluting segment of the nephron (1-4); however, no one has conclusively demonstrated that a sustained positive water balance in the adrenal-insufficient patient completely inhibits the secretion of antidiuretic hormone (ADH). Although osmotic inhibition of the release of ADH may be normal in adrenal insufficiency, the human or animal in this state may have a distorted "volume" stimulus that prevents complete inhibition. Recent studies have demonstrated that contraction or redistribution of both vascular and extracellular volumes can cause the continued secretion of ADH in the water-loaded subject (5, 6). Blood loss, quiet standing, venous congestion of the lower extremities, and positive pressure breathing are all events that may produce this contraction or redistribution.Since the adrenal-insufficient patient is hypotensive. has poor vascular reactivity, and exhibits a redistribution of body fluids (7-9), it seems reasonable to assume that a distorted volume stimulus for release of ADH might contribute to his impaired water diuresis. If this were true, it might be possible to improve the water diuresis by an appropriate expansion of either the extracellular or vascular compartment before or during a water load. This was attempted in the present study.

“…Such an increase in urinary solute is known to augment the diuresis resulting from administration of large water loads (14,15,(19)(20)(21)(22). Moreover, when the magnitude of diuresis in water-loaded subjects is enhanced by increasing the solute load, the concentration of total solute characteristically rises (22,23). On the other hand the rise in solute output during steroid administration, when it occurred, was so small compared to the increase in urine flow that solute concentration fell.…”

Section: Fig 3 Changes In Glomerular Filtration Rate (Cin) During Hmentioning

confidence: 99%

The Effects of Cortisone and Hydrocortisone on Water Diuresis and Renal Function in Man

Raisz¹,

McNeely²,

L³

et al. 1957

The deficient diuretic response to water which is characteristic of patients with adrenal insufficiency can be rapidly corrected by the administration of cortisone (1-3). The mechanism of the defective diuresis and the precise nature of the response to hormonal replacement have not been established. A number of observations, chiefly in experimental animals, have suggested that administration of various adrenocortical preparations in large "pharmacologic" doses also influences water diuresis in the normal organism (4). However, no systematic study of the latter effect has been made in man. The present report describes the effects of large doses of cortisone and hydrocortisone on water diuresis, renal solute excretion, glomerular filtration rate, and effective renal plasma flow in man. Striking augmentation of the maximal rates of urine flow observed during maintained water loading was a regular occurrence. The steroids studied appear to have a specific influence upon water reabsorption by the renal tubules, an action which can be separated from their effect on renal hemodynamics. MATERIALS AND METHODSThe subjects were adult male patients free from cardiovascular, renal and endocrine disease. Three sets of studies concerning water diuresis were carried out.Group I-A-Intermittent studies during prolonged intramuscular administration of cortisone. In these experiments creatinine clearance was measured, but not inulin or para-aminohippurate clearances. Urinary total solute concentration was calculated from determined cations and urea; freezing point determinations were not made.1 Present address: Veterans Administration Hospital, Syracuse, New York.Group I-B--Serial studies at intervals of one to three days during prolonged oral cortisone and hydrocortisone administration. Clearances of inulin and para-aminohippurate, as well as of creatinine, were determined. Urinary osmolality was measured cryoscopically.Group II-The acute response to intravenous infusion of hydrocortisone during water diuresis. Renal clearances and urinary total solute concentrations were measured as in I-B.Details of experimental procedure will be given together with the results in each group. Chemical methods and calculationsUrine and serum were analyzed for sodium, potassium, chloride and creatinine by methods previously described (5). Serum creatinine was determined after adsorption on Lloyd's reagent (6). Total solute concentration in urine and serum was measured by freezing point depression using a Fiske osmometer (Advanced Instruments, Inc., Needham, Mass.