Posterior Pituitary Vasopressin Research Articles

Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice

This study increases our understanding of the mechanisms leading to vasopressin release under conditions of water restriction (acute dehydration). Specifically, these studies suggest that the aldose reductase-fructokinase pathways may be involved in vasopressin synthesis in the hypothalamus and secretion by the pituitary in response to acute dehydration. Nevertheless, mice undergoing water restriction remain capable of maintaining sufficient vasopressin (copeptin) levels to allow normal urinary concentration. Further studies of the aldose reductase-fructokinase system in vasopressin regulation appear indicated.

The Effect of the Administration of Water or Isotonic Nacl Solution on the Urinary Excretion of 5-Hydroxyindoleacetic Acid in the Rat

AbstractAdministration of tap water by stomach tube or of isotonic NaCl solution orally or subcutaneously produces a conspicuous increase in the urinary excretion of 5-hydroxyindoleacetic acid (5-hiaa) in the rat. The same increase can be observed after administration of water plus posterior-pituitary antidiuretic hormone (adh). Tap water is less effective than physiological saline; the latter, in its turn, is more effective by the subcutaneous route than by mouth. Increase of 5-hiaa may be, for short periods, as high as 3 times normal. The minimum oral dose of tap water causing a significant increase in urinary 5-hiaa is 2 ml./100 g., that of physiological saline 1 ml./100 g. Repeated doses of both tap water and physiological saline produce a more intense and long-lasting increase of 5-hiaa output than single doses. Generally, excess 5-hiaa coincides with excess urine elimination, but there is no obligatory correlation of the intensity of the two phenomena. Recovery, as urinary 5-hiaa, of exogenous 5-hiaa, 5-hydroxytryptamine (5-ht) and 5-hydroxytryptophan (5-htp) is the same in control, non-hydrated rats and in rats given single or repeated doses of tap water, tap water plus adh, or isotonic saline solution. The mechanism by which water or saline administration produces increased urinary excretion of 5-hiaa is discussed.

Alterations in the central vasopressin and oxytocin axis after lesion of a brain osmotic sensory region

The anteroventral region of the third ventricle (AV3V) is critical in mediating osmotic sensitivity. AV3V lesions increase plasma osmolality and block osmotic-induced vasopressin (VP) and oxytocin (OT) secretion. The aim was to evaluate the effects of AV3V lesions on neurosecretion under control/water replete conditions and after 48 h dehydration. The focus was on central peptidergic changes with measurement of OT and VP content in the hypothalamic paraventricular (PVN) and supraoptic (OT) regions and the posterior pituitary. AV3V-lesioned rats exhibited an elevated plasma osmolality and higher OT content in SON and PVN. There was an increase in VP content in PVN, but no change in SON. As predicted, the plasma peptide response to dehydration was absent in lesioned animals. However, dehydration produced depletion in posterior pituitary VP in lesioned animals with no change in OT. No changes in nuclear VP and OT levels were seen after dehydration. These results demonstrate that AV3V lesions alter the VP and OT neurosecretory system, seen as a blockade of osmotic-induced release and an increase in basal nuclear peptide content. The data indicate that interruption of the osmotic sensory system affects the central neurosecretory axis, resulting in a backup in content and likely changes in synthesis and processing.

Effect of age and testosterone on the vasopressin and aquaporin responses to dehydration in Fischer 344/Brown-Norway F1 rats.

To determine if the aging-associated decline in testosterone results in attenuated vasopressin (VP) responses to dehydration, testosterone implants were given to aged male Fischer 344Brown-Norway F1(F344BNF1) rats. Water deprivation caused comparable dehydration, increased plasma VP (pVP), and decreased posterior pituitary (PP) VP content in 4-, 15-, and 28-month-old rats. Dehydration increased VP mRNA content of supraoptic nuclei only at 4 months, whereas VP mRNA length was increased at both 4 and 15 months of age. The elevated pVP in the water-deprived aged rats indicates that even without an increase in VP mRNA content, PP VP storage was adequate to maintain elevated pVP. Dehydration increased aquaporin-2 content at 4, but not at 15 or 28 months of age, suggesting decreased renal responsiveness to VP. Testosterone replacement did not produce dehydration-induced increases in VP mRNA or aquaporin-2. Therefore, testosterone deficiency does not result in altered VP responses to dehydration in aged F344BNF1 rats.

Dehydration induces Fos, but not increased vasopressin mRNA in the supraoptic nucleus of aged rats

Dehydration induces Fos expression and increases the length of the vasopressin (VP) mRNA poly-A tail and the content of Vp mRNA in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus. The current studies were performed to evaluate the effect of aging on these responses. Fischer 344 rats of 4, 14, and 28–30 months of age were either water deprived for 72 h or allowed ad libitum access to water. Fos induction in the SON and PVN was examined by immunocytochemistry in order to provide an index of cellular activation. VP mRNA content and size was examined in SON by Northern analysis as an index of VP synthetic capacity. Dehydration induced the expected increase osmolality in all three ages, however, serum VP was only increased in the 4- and 14-month-old rats. The increase in serum VP was accompanied by a decrease in VP content of the posterior pituitary (PP) in the dehydrated 4- and 14-month-old rats. PP VP content was reduced in both the hydrated and dehydrated old rats relative to the other ages (P = 0.0007). Fos was induced in both SON and PVN of all water deprived rats regardless of age. The density of Fos staining was increased in both nuclei following dehydration (SON,P = 0.002; PVN,P = 0.0001). There was also a significant increase in the number of cells expressing Fos in both nuclei in the dehydrated animals (SON,P = 0.0022; PVN,P = 0.0056). There was no significant effect of age on the density of Fos staining. In contrast, dehydration failed to elicit the expected increase in VP mRNA size and content in the SON of the aged dehydrated rats although both of these parameters were increased in the 4- a and 14-month-old rats (P<0.05). Thus, the inability of old Fischer rats to increase serum VP during chronic dehydration is not caused by decreased activation of the neurons (as indicated by Fos induction), but apparently reflects depletion of PP stores of VP due to an inability to increase the amount of VP mRNA available for translation.

Control of posterior pituitary vasopressin content: implications for the regulation of the vasopressin gene

Control of posterior pituitary vasopressin content: implications for the regulation of the vasopressin gene

Fluoxetine induces vasopressin and oxytocin abnormalities in food-restricted rats given voluntary exercise: relationship to anorexia nervosa

Anorexia nervosa is associated with vasopressin, oxytocin and serotonin abnormalities. Because of the relationship between exercise and anorexia nervosa, we explored the weight-loss syndrome produced by wheel running in food-deprived rats. Its effects on regional vasopressin and oxytocin concentrations were determined under basal conditions and following systemic fluoxetine. Weight-matched, exercised and unexercised rats served as controls. Fluoxetine caused abnormalities in suprachiasmatic vasopressin and dynorphin A content and in thymus oxytocin content that did not occur in weight-matched or exercised controls. No syndrome-specific anomalies occurred in the hypothalamo-neurohypophysial system or dorsal vagal complex (DVC). However, weight reduction and fluoxetine increased circulating vasopressin; moderate exercise caused fluoxetine-induced elevations in posterior pituitary vasopressin and oxytocin; and, unlike the other groups, fluoxetine increased DVC oxytocin in freely fed unexercised rats. It was concluded that syndrome-specific vasopressin and oxytocin abnormalities occur that are not secondary to weight loss or moderate exercise; that weight loss or fluoxetine increases circulating vasopressin; that moderate exercise alters neurohypophysial vasopressin and oxytocin content; and that weight loss or exercise inhibits a fluoxetine-stimulated increase in DVC oxytocin. Finally, it was argued that the fluoxetine abnormalities indicate possible serotonin dysfunction in the syndrome.

Cause of excessive drinking in diabetes insipidus.

DAMAGE to the posterior lobe of the pituitary gland or in the region of the tuber cinereum of the hypothalamus causes diabetes insipidus, characterized by excessive drinking (polydipsia) and excessive production of urine (polyuria). Because both these effects are controlled by administration of posterior pituitary antidiuretic hormone which is known to act on the kidneys, it has been supposed that the polydipsia in diabetes insipidus is secondary to the polyuria caused by lack of antidiuretic hormone. Evidence for this view comes from experiments carried out by Richter and Eckert in 1935. They found that after removal of the posterior lobe of the pituitary gland in rats the resulting polydipsia is eliminated by tying both ureters to prevent urine formation1. When urination is prevented in rats with diabetes insipidus caused by hypothalamic lesions, however, the results are not so straightforward. Electrolytic lesions made with a nichrome electrode at the base of the tuber cinereum, which invariably gave rise to diabetes insipidus in rats with their kidneys present, also slightly increased the water intake in rats with both kidneys removed2. Such an excess drinking in diabetic rats without kidneys (primary polydipsia) would be important if, as Smith and McCann suggested, it could be shown to result from damage to a hypothalamic “thirst satiety centre” responsible for stopping drinking when sufficient water had been drunk to satisfy the body's needs.

Use of Diuretics in the Treatment of Obesity

To the Editor:— In an article entitled A New Concept in the Treatment of Obesity ( JAMA 185 :50 [Oct 5] 1963) by Gordon and co-workers, the following statement is made: ... obese human subjects have a diminished glomerular filtration rate, an elevated titer in blood, of posterior pituitary antidiuretic hormone (ADH), and a markedly reduced renal clearance of water. In addition, they manifest a defect in renal clearance of sodium.... Accordingly, the authors advocate the use of diuretics and mild restriction of salt in the treatment of obesity. The curve of weight loss in the vast majority of obese individuals in negative caloric balance is not linear, but is a series of ups and downs with frequent periods of no apparent weight change. As has been demonstrated, these irregularities are intimately associated with the storage and release of relatively large quantities of water. The fact that both retention and release of

The antidiuretic hormone (ADH) and heart insufficiency. 1. Comparative evaluation of methods of extracting ADH from human urine and isolation of antidiuretic hormones by paper electrophoresis

Part I. Comparative evaluation of the extracting method of antidiuretic hormone from human urine, dan purification of commercial posterior pituitary hormone and extracted urinary antidiuretic substance by means of paper electrophoresis.In order to clarlify the role of the posterior pituitary antidiuretic hormone for the accumulation or conservation of fluid in the body under various clinical conditions, the auther reexamined previously reported extracting methods of antidiuretic substance from urine and chiefly compared the method by Noble & Rindernechit with that of Grollman & Woods with regard to the reliability and recovery.Next investigative approach was to purify the extracted substance from urine by the Noble & Rindernechit's method for a comparison of commercial posterior pituitary antidiuretic hormones by means of paper electrophoresis, and to determine whether the purified material was of posterior pituitary origin.Tne results are concluded as follows : 1) Absorptive method of Noble & Rindernechit, employing zinc ferrocianide, gave constant and satisfactory recovery in extracting antidiuretic hormone from urine, that is, average recovery rate of 85.6% for concentration of antidituretic hormone (Pitressin) I mu./cc to 0.1mu./cc, 68% for concentration of 20μu, /cc to 2μu./cc of urine.On the other hand absorptive method of Grollman & Woods employing active charcoal gave unstable and poor recovery.2) Urinary extracts by adsorption on zinc ferrocianide, on active charcoal, and commercial posterior pituitary hormones can be satisfactorily purified by means of paper electrophoresis under constant voltage of 400V/25cm. in 1.15N acetic acid solution.3) Under the same condition Pituitan (commercial posterior pitutary hormone) can be separated into 8 fractions, extract employing zinc ferrocianide in 7 fractions, active charcoal 10-11 fractions.4) Fraction which has antidiuretic and pressor activity in commercial posterior pituitary hormones and urinary extracts has the same migration distance as the 6th fraction in Pituitan from anode under the above described condition.5) Antidiuretic activity of the fraction markedly increases in the urine of normal subjects after the administration of hypertonic saline solution, and also in diabetes insipidus patients' urine after the administration of the posterior pituitary antidiuretic hormones.

The Role of Antidiureric Hormone in Congestive Heart Failure

Part II. Urinary antidiuretic hormone (ADH) and congestive heart failure.A clinical entity, congestive failue has been subjected to physiologic reinterpretation. This reinterpretation has been due for the most part to the fact that this entity is one involving a complex series of events occuring over a considerable period of time between the initiating factors and the final remarkable condition of the edematous state and there is no direct correlation between initiating factors and final condition.It is no doubt that the edema is a state of abnormal retention and distribution of Na and water in the decreased their excretion from kidney, therefore many investigators emphasized the role of the kidney in the development of congestive failure, and impaired glomerular filtration has been considered principal renal abnormality. Lately many peports has pointed out the abnormal function of the kidney tubules, and this in turn admitt the humoral factors which control the reabsorption of Na and water.As regard to the Na reabsorption aldosterone play an important role and evidence has shown that in congestive failure it's excretion is much greater than normal. On the other hand posterior pituitary antidiuretic hormone (ADH) is the potent water conservatory hormone and control water reabsoption in the kidney.In spite of many researchs, we are far from a final conclusion in regard to the role of posterior pituitary hormone. In the pervisous literature author has reported the reliable extraction and estimation method of this hormone from urine.Employing this method hospitalized valvular, congenital heart failure in various grade were used for the estimation of urinary antidiuretic hormone (ADH), and observed the changing pattern of ADH under the treatment of digitalis and diuretics. Secretion mechanism of ADH was examined by water load. Inactivation of ADH in the serum of congestive failure was compaired to liver cirrhosis and using portal vein constricted rabits.The conclusions thus obtained as follows.1) Urinary excretion of ADH in congestive heart failure were remarkably increased than the normal subject and as the grade of failure advance ADH increased.2) There was no direct correlation between the ADH excretion and the initial diuresis which was caused by the digitalis and diuretic therapy, but as the congestive failure improve urinaly ADH decreased.3) In contrast with normal subject no decrease or disappearance in urinary ADH was found after the administration of water in congestive failure. This in turn, proved

POSTERIOR PITUITARY ANTIDIURETIC HORMONE AND TOXÆMIA OF PREGNANCY

Medical Journal of AustraliaVolume 2, Issue 13 p. 523-523 Comment and Abstract POSTERIOR PITUITARY ANTIDIURETIC HORMONE AND TOXÆMIA OF PREGNANCY First published: 01 September 1961 https://doi.org/10.5694/j.1326-5377.1961.tb69749.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume2, Issue13September 1961Pages 523-523 RelatedInformation

Hypothalamo-neurohypophysial involvement in the corticotrophic action of acetylcholine.

Acetylcholine produced a fall of blood eosinophils and adrenal ascorbic acid in normal rats; these effects did not occur in hypophysectomized animals or in hypophysectomized animals bearing a pituitary homotransplant in the anterior chamber of the eye. Acetylcholine had a striking and long-lasting antidiuretic effect in normal rats, which was abolished by hypophysectomy. In normal dogs, intravenous injections of acetylcholine raised the concentration of posterior pituitary antidiuretic hormone in the cerebrospinal fluid. These results are discussed in connexion with the hypothesis that posterior pituitary antidiuretic hormone may be the neurohumoral substance involved in the hypothalamic control of the anterior pituitary.

An assay method for antidiuretic hormone based on a more specific response index.

INTRODUCTION Numerous methods have been proposed over the past 25 years for the assay of posterior pituitary antidiuretic hormone (A.D.H.). Many of these have recently been reviewed by Stein (1952). Most of the methods can be classified in two categories according to the type of index of response used. One category includes the methods in which increment in urinary excretion of an individual solute, usually chloride, has been related to the A.D.H. content of the administered material (Anselmino, 1932; Ham, 1942, 1943; Ralli, 1950). The second category consists of methods where the index of response is change in rate of urine flow (Gibbs, 1930; Burn, 1931; Theobald, 1934; Oilman, 1937; Walker, 1939; Robinson, 1940; Jeffers, 1942; Birnie, 1950; Ames, 1950; Stein, 1952; Ginsburg, 1953; Dicker, 1953). Neither of these response indices can be considered specific. Increments in urinary solute excretion, particularly chloride and sodium, are only indirectly related to A.D.H. action (Leaf, 1953).

The secretion of antidiuretic hormone in response to haemorrhage and the fate of vasopressin in adrenalectomized rats.

SUMMARY 1. The antidiuretic potency of arterial blood from adrenalectomized rats was greater than that from intact rats, but only if 2 or more ml. of blood were taken from each rat. It is concluded that the amounts of posterior pituitary antidiuretic hormone released during haemorrhage are greater in adrenalectomized than in intact rats. 2. The effect of haemorrhage on the antidiuretic potency of blood in adrenalectomized rats treated with sodium chloride or cortisone was not different from that in intact rats. 3. The disappearance of intravenously injected vasopressin (100 mU/100 g body weight) was retarded after adrenalectomy. Up to 48 hr after adrenalectomy this was due to a reduced capacity of the kidneys to remove vasopressin from the circulation. 4. Treatment with cortisone increased the rate of disappearance of vasopressin in adrenalectomized rats, but the rate was not restored to that observed in intact animals. 5. Treatment with sodium chloride did not affect the rate at which vasopressin was removed from the circulation of adrenalectomized rats. 6. The excretion of an antidiuretic agent in the urine which followed intravenous injection of vasopressin (100 mU/100 g) 48 hr after adrenalectomy was equivalent to 2·1% of the dose. This compared with an excretion of 6·7% of the dose in intact animals.

Studies in nephrosis: chemical corticoids, salt-retaining factor, and effect of ACTH.

THE accumulation of edema fluid in patients suffering from the nephrotic syndrome, and the mechanism of its production, have been the subject of considerable speculation and research. According to Barnett (1) who has recently reviewed existing knowledge of the pathogenesis of this type of edema, there is evidence that a glomerular-tubular imbalance exists in the kidney in the nephrotic state. The preponderance of tubular function may depend on relatively decreased glomerular function, due either to pathologic lesions in the glomeruli or to “circulatory insufficiency” secondary to decreased serum osmotic pressure. Alternatively, it may indicate true tubular overfunction in response to excessive stimulation by posterior pituitary antidiuretic hormone, or adrenocortical salt-retaining hormone. The present study was undertaken with the object of further investigating adrenal function in this disease. The excretion of various types of corticoids is only a very indirect measure of adrenocortical function and is...

Diuresis and antidiuresis in kidneys autotransplanted to the neck of dogs.

1. The water diuretic responses of dog kidneys autotransplanted to the neck have been studied. In the presence of a normal kidney the “neck” kidney for one or two weeks following operation shows a normal diuretic response following an oral water load. Between two and four weeks after transplantation the diuretic response falls to half or less than half of the normal kidney and then remains fairly constant over many months. On removal of the normal kidney the “neck” kidney regains a normal diuretic response to water.2. From the time of transplantation the “neck” kidney excretes urine of low specific gravity.3. The “neck” kidney retains a normal response to posterior pituitary antidiuretic hormone.4. In the “neck” kidney the antidiuretic response to faradic stimulation is unaltered from the normal.

The inactivation of posterior pituitary antidiuretic hormone by liver extracts.

INACTIVATION of the posterior pituitary antidiuretic hormone at some site in the body has been postulated by Ingram, Ladd and Benbow (1939) on the basis of the small amount excreted after injection of posterior pituitary preparations. The in vitro inactivation studies of Heller and Urban (1935) and the in vivo observations of Eversole, Birnie and Gaunt (1949) support the existence of such a system and indicate that the greatest activity is found in liver tissue. The inactivation of other posterior pituitary fractions, namely, the oxytocic (Gulland and Macrae, 1933) and pressor (Moller-Christensen, 1951) by the tissues have been reported. These reports, however, have not described the nature of the inactivating system. The present investigation was undertaken for the purpose of securing additional information regarding the nature of the system in rat liver homogenates which inactivates posterior pituitary antidiuretic hormone. Some of these observations have-been reported in an earlier abstract (Birnie, 19...

The action and fate of vasopressin in newborn and infant rats.

Estimations of urine volumes and inulin U/P ratios in newborn rats after the administration of 4·5 ml. water and 10 mU. vasopressin/100 g. body weight failed to show an antidiuretic response comparable to that produced in adult controls. When body surface was chosen as the basis of dosage, relatively larger amounts of water were given to newborn rats. These produced an increase in the rate of urine flow (which, however, still remained well below the adult level), but an inhibitory effect of vasopressin again could not be demonstrated. Experiments on older rats (up to 4 weeks of age) showed that an antidiuretic effect of vasopressin comparable to that of adults develops only after several weeks of postnatal life, approximately at the same time as a full diuretic response to water could be obtained. When 10 mU. vasopressin/100 g. body weight was injected both adult and newborn rats excreted about 10% of this dose. It is suggested that vasopressin acts less effectively in newborn rats because for some time after birth the kidney is less responsive to the posterior pituitary antidiuretic hormone than in adults.

Mechanisms of ascites formation

Dr. Frederick K. Heath: The development of ascites in patients with cirrhosis of the liver has long been correlated with portal hypertension and hypoalbuminemia. The manner in which these and other factors may contribute to this process is considered in this clinic. In the otherwise normal animal obstruction to the hepatic outflow (hepatic veins or vena cava) produces ascites but occlusion of the portal system results in the development of collateral circulation and hypersplenism. Portal hypertension alone, then, may furnish a larger vascular bed for diffusion and because of stasis may also tend to render this area more permeable. While both conditions are favorable to ascites formation, they do not of themselves produce it. The role of the lymphatics has not been determined. On this background osmotic forces operate. The net hydrostatic pressure (capillary blood pressure minus ascitic hydrostatic pressure) tending toward the formation of ascites is opposed by the net colloid pressure (plasma colloid osmotic pressure minus ascitic colloid osmotic pressure). Dr. Mankin showed that in the presence of ascites, irrespective of whether it was increasing or decreasing, the difference between the capillary and ascitic colloid osmotic pressures remains fairly constant. This state of dynamic equilibrium between opposing forces need be only slightly altered to influence the direction of fluid flow before equilibrium is regained. Thus mercurial diuresis, presumably by hemoconcentration, tends to decrease ascites. In the same fashion intravenous albumin may or may not decrease ascites depending upon how rapidly it diffuses from plasma to the ascitic compartment. Of great interest is the finding that patients with ascites do not excrete sodium in the urine proportionally to their intake. The magnitude of this deficiency would appear to correlate with the degree of ascites and the deficiency in serum sodium levels. Ingested sodium is almost entirely diverted to the ascitic fluid which tends to increase when the daily intake of sodium chloride exceeds 1 gm. However, if salt be restricted to about 1 gm. daily, water excretion rises, serum protein values slowly increase, serum sodium concentration remains constant and no further ascitic fluid is formed. In this fashion progression of this phase of the disease may be interrupted. About one-half of Dr. Kunkel's patients maintained on low-sodium diets over a period of six months regained their ability to excrete sodium normally and concomitantly showed improvement in their ascites. Dangerous depletion of sodium has been observed on this regimen in the presence of renal damage or following the use of mercurial diuretics. Similar to the depression in the urinary excretion of sodium, Dr. Ralli described a marked reduction in water output in cirrhotic patients with ascites. She has proposed that the renal abnormality may be due to greater tubular reabsorption of water dependent upon an increase in the posterior pituitary antidiuretic hormone and has reported finding unusual amounts of antidiuretic substances in the urine of ascitic patients. According to this evidence, the disappearance of ascites without change in hypoalbuminemia becomes understandable. While the relative importance of these mechanisms undoubtedly varies from patient to patient and cannot be determined in advance so as to indicate a single line of therapy, they nevertheless suggest several special therapeutic approaches such as are indicated in the clinic.