Studies on Alcohol Diuresis. Ii. The Evaluation of Ethyl Alcohol as an Inhibitor of the Neurohypophysis 12

Rubini, Milton E.; Lamdin, Ezra; Epstein, Franklin H.

doi:10.1172/jci103093

Cited by 130 publications

(28 citation statements)

References 11 publications

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“…However, in the present investigation, free water clearance was not a constant for any one individual but actually increased with increasing dietary intake and urinary excretion of solute (Figure 4). Similar changes in CH2o were noted by Rosenbaum and his associates (8) in experiments in which solute excretion was varied during water diuresis, by Welt, Young, Thorup, and Burnett (14) following the administration of a carbonic anhydrase inhibitor to subjects with maximal water diuresis, and in previous experiments from this laboratory (15). This rise in CH2o can be adequately explained by the reabsorption of additional solute in hypertonic solution, when further isosmotic fluid is delivered to the distal tubule.…”

Section: Discussionsupporting

confidence: 79%

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

Kleeman¹,

Epstein²,

White³

1956

J. Clin. Invest.

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A sustained positive load of water administered to a normal subject results in maximal water diuresis associated with a minimal concentration of solutes in the urine. The term "physiological diabetes insipidus" has been applied to this situation, because under these circumstances, the release of antidiuretic hormone from the posterior pituitary is inhibited and as a consequence, that part of the water of glomerular filtrate that is normally reabsorbed under the influence of this hormone is excreted. During sustained water diuresis, therefore, variations in urinary flow, urinary osmolarity, and "free water clearance" (CH2o) (1) might be ascribed to factors other than antidiuretic hormone.In the present study, the effect of variations within the physiological range of solute load, dietary composition and endogenous creatinine clearance upon these parameters were investigated in normal subjects in a state of "physiological diabetes insipidus," in whom the level of circulating antidiuretic hormone was presumably at a minimum. The results indicate that both glomerular filtration rate (endogenous creatinine clearance) and solute load have important and statistically separable effects on the characteristics of water diuresis. MATERIALS AND METHODSTwenty-nine experiments were performed on fourteen healthy young male medical students and physicians. After a light breakfast at 7:00 A.M. the experiment was begun at about 8:30 A.M. and varied in length from 3-12 to 5-½ hours. The subjects remained in the semirecumbent position throughout, getting up only to void.In twelve paired experiments on six subjects a "highsolute diet" or a "low-solute diet" was ingested for three days prior to the experiment. The "high-solute diet" contained approximately 150 grams of proteins and 10 to 15 grams of salt; the "low-solute diet" contained less than 25 grams of protein and 5 grams of salt. In all other experiments diet was uncontrolled. Subjects drank 1 Supported by United States Public Health Service Grants A-625 and H-834. one liter of water upon reclining. A sustained positive balance of one liter was maintained throughout the rest of the experiment by oral ingestion of water and by the infusion of 2.5 per cent fructose in water at rates below that necessary to produce glycosuria when tested with Benedict's solution.Sodium, potassium and chloride in serum and urine were measured by methods previously described (2, 3). Creatinine in serum and urine was determined by a modification of the method of Hare (4). Endogenous creatinine clearance was used to approximate glomerular filtration rate. Urea in serum and urine was measured by a micro-diffusion technique (5); and the osmolarity of serum and urine was measured by freezing point depression using a Fiske osmometer. These results are obtained in milliosmols per kilogram of water. Free water clearance (CH2o) was calculated as the difference between urinary flow V and osmolar clearance: CH,o=

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Section: Discussionsupporting

confidence: 79%

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

Kleeman¹,

Epstein²,

White³

1956

J. Clin. Invest.

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“…Certainly in the waterloaded normal subject who is in a state of "physiologic diabetes insipidus" it is reasonable to assume that no circulating ADH is present. The validity of this assumption is supported by the observation that in such subjects the administration of alcohol, a powerful inhibitor of ADH, does not enhance urine flow (30), an observation that we have confirmed in a number of subjects, including B.C. of the present study.…”

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

confidence: 78%

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

Raisz¹,

McNeely²,

L³

et al. 1957

J. Clin. Invest.

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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.

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“…One possible explanation for this observation is that nicotine may release ACh through the nicotinic receptor from presynaptic choli nergic terminals on the neurons in the nuclei as demonstrated recently in a synaptosomal preparation of the myenteric plexus (26) In the present experiments, animals were loaded with water and ethanol in order to keep the urine outflow constant and at a measurable flow rate. As a lower extracellular osmotic pressure with water loading (27) and ethanol-anesthesia are known to inhibit the neurons in these nuclei (15,28), the true effective concentrations for oxotremorine in unanesthetized animals without water and ethanol-loading could be lower than the apparent values estimated above.…”

Section: Discussionmentioning

confidence: 82%

Antidiuretic Effects of Oxotremorine Microinjected into the Hypothalamic Supraoptic and Paraventricular Nuclei in a Water-Loaded and Ethanol-Anesthetized Rat

Tsushima

Mori

Matsuda

1984

Japanese Journal of Pharmacology

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Abstract-The effect of oxotremorine, a muscarinic agonist, on urine outflow compared with the effects of other cholinergic agonists and inhibitory effects of cholinergic antagonists upon the cholinergic actions were studied by microinjecting drugs stereotaxically, unilaterally into the supraoptic (SON) or paraventricular nuclei (PVN) in the hypothalamus of the rat which was loaded with water and anesthetized with ethanol. Oxotremorine decreased the urine outflow in dose and time-dependent manners when microinjected into these nuclei. The median effective doses (ED50) were approx. 0.3 and 0.2 nmol in SON and PVN, respectively, being much less than ED50 values for nicotine. The time course of the antidiuretic effects was relatively slow, with the minimal urine outflow at approx. 30 min and the duration of one or longer hours. The antidiuretic effects of oxotremorine in these nuclei as well as the effects of acetylcholine and nicotine were completely blocked by pretreatment with atropine.

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Studies on Alcohol Diuresis. Ii. The Evaluation of Ethyl Alcohol as an Inhibitor of the Neurohypophysis 12

Cited by 130 publications

References 11 publications

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

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

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

Antidiuretic Effects of Oxotremorine Microinjected into the Hypothalamic Supraoptic and Paraventricular Nuclei in a Water-Loaded and Ethanol-Anesthetized Rat

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