pituitrin and Nephrotic-Syndrome

The pathologic consequences of sodium retention in the CKD population can lead to hypertension, edema, and progressive disease. Sodium excess is responsible for increases in oxidative stress, which alters kidney vasculature. As progression of CKD occurs, hyperfiltration by remaining nephrons compensates for an overall decrease in the filtered load of sodium. In the later stages of CKD, compensatory mechanisms are overcome and volume overload ensues. Nephrotic syndrome as it relates to sodium handling involves a different pathophysiology despite a common phenotype. Extrarenal sodium buffering is also examined as it has significant implications in the setting of advanced CKD.

Topics: Animals; Atrial Natriuretic Factor; Diet, Sodium-Restricted; Homeostasis; Humans; Hypertension; Nephrotic Syndrome; Oxidative Stress; Renal Insufficiency, Chronic; Renin-Angiotensin System; Skin; Sodium; Sympathetic Nervous System; Vasopressins

Water excretion is regulated in large part through the regulation of osmotic water permeability of the renal collecting duct epithelium. Water permeability is controlled by vasopressin through regulation of the water channel, aquaporin-2 (AQP2). Two processes contribute: (1) regulation of AQP2 trafficking to the apical plasma membrane; and (2) regulation of the total amount of the AQP2 protein in the cells. Regulation of AQP2 abundance is defective in several water-balance disorders, including many polyuric disorders and the syndrome of inappropriate antidiuresis. Here we review vasopressin signaling in the renal collecting duct that is relevant to the two modes of water permeability regulation.

Topics: Animals; Aquaporin 2; beta Catenin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Heart Failure; Humans; Inappropriate ADH Syndrome; Kidney Tubules, Collecting; Liver Cirrhosis; Mice; Myosin-Light-Chain Kinase; Nephrotic Syndrome; Permeability; Phosphoproteins; Phosphorylation; Polyuria; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-jun; Rats; Signal Transduction; Transcription Factor AP-1; Transcription Factors; Vasopressins

The collecting duct is the site of final Na reabsorption according to Na balance requirements. Using isolated rat cortical collecting ducts (CCD) and mpkCCD(cl4) cells, a mouse cortical collecting duct cell line, we have studied the physiological control of Na,K-ATPase, the key enzyme that energizes Na reabsorption. Aldosterone, a major regulator of Na transport by the collecting duct, stimulates Na,K-ATPase activity through both recruitment of intracellular pumps and increased total amounts of Na pump subunits. This effect is observed after a lag time of 1 hour and is independent of Na entry through ENaC, but requires de novo transcription and translation. Vasopressin and cAMP, its second messenger, stimulate Na,K-ATPase activity within minutes through translocation of Na pumps from a brefeldin A-sensitive intracellular pool to the plasma membrane. Dysregulation of collecting duct Na,K-ATPase activity is at least in part responsible of the Na retention observed in nephritic syndrome. In this setting, Na,K-ATPase activity and subunit synthesis are specifically increased in CCD. In conclusion, aldosterone, vasopressin, and intracellular Na control the cell surface expression of Na,K-ATPase and translocation from intracellular stores is a major mechanism of regulation of Na,K-ATPase activity in collecting duct principal cells.

Topics: Aldosterone; Animals; Cyclic AMP; Humans; Kidney Tubules, Collecting; Mammals; Models, Biological; Nephrotic Syndrome; Sodium; Sodium-Potassium-Exchanging ATPase; Vasopressins

Topics: Blood Volume; Combined Modality Therapy; Heart Failure; Humans; Hyponatremia; Inappropriate ADH Syndrome; Liver Cirrhosis; Nephrotic Syndrome; Vasopressins

Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome and pregnancy. In recent years the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation.

Topics: Blood Volume; Cardiac Output; Cardiac Output, Low; Edema; Female; Fibrosis; Humans; Kidney; Natriuresis; Nephrotic Syndrome; Pre-Eclampsia; Pregnancy; Renin-Angiotensin System; Sympathetic Nervous System; Vascular Resistance; Vasodilation; Vasopressins

Edema is a collection of fluid within the body's interstitial space which occurs when there is an alteration of the Starling forces which control transfer of fluid from the vascular compartment to surrounding tissue spaces. Generalized edema results when altered Starling forces affect all capillary beds, such as occurs in cardiac failure, cirrhosis, and nephrotic syndrome. Common to these conditions is the development of increased total body sodium and water content. The kidneys play an essential role in the retention of this sodium and water. In this article we shall discuss the signals the kidneys receive for sodium and water retention in these edematous disorders (afferent mechanisms). We shall also examine the means by which the kidney responds to these signals and retains sodium and water (efferent mechanisms). As shall become apparent these edematous states may share many of the same afferent and efferent mechanisms for sodium and water retention.

Topics: Blood Volume; Body Water; Cardiac Output; Edema; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Liver Cirrhosis; Nephrotic Syndrome; Renal Circulation; Renin-Angiotensin System; Sodium; Vasopressins

Nonsteroidal antiinflammatory drugs can adversely affect the kidney. They may induce sodium retention and antagonize the action of diuretics, impair free-water clearance and cause hyponatremia, and prevent aldosterone production and cause hyperkalemic hyperchloremic acidosis. If patients taking these drugs are exposed to a renal insult, acute renal failure becomes more likely. Similarly, patients with chronic renal disease who are taking them appear to be at greater risk of chronic renal failure. However, not all renal effects of nonsteroidal antiinflammatory drugs are adverse. Beneficial effects have been reported in patients with Bartter's syndrome and in those with severe orthostatic hypotension.

Topics: Acidosis; Acute Kidney Injury; Aged; Anti-Inflammatory Agents; Bartter Syndrome; Female; Humans; Hyponatremia; Hypotension, Orthostatic; Ibuprofen; Indomethacin; Kidney; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Nephrotic Syndrome; Prostaglandin Antagonists; Sodium; Vasopressins

Topics: ACTH Syndrome, Ectopic; Humans; Lung Neoplasms; Nephrotic Syndrome; Paraneoplastic Syndromes; Renin; Vasopressins; Water-Electrolyte Imbalance

The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

Topics: Acute Disease; Analgesics; Humans; Hypercalcemia; Immune System Diseases; Kidney Calculi; Kidney Concentrating Ability; Kidney Diseases; Kidney Tubular Necrosis, Acute; Necrosis; Nephrosis; Nephrotic Syndrome; Potassium Deficiency; Proteins; Tetracyclines; Ureteral Diseases; Ureteral Obstruction; Urologic Neoplasms; Vascular Diseases; Vasopressins

Topics: 17-Hydroxycorticosteroids; Adrenal Cortex; Adrenal Glands; Adrenocorticotropic Hormone; Anorexia Nervosa; Blood Glucose; Brain Diseases; Catecholamines; Child; Circadian Rhythm; Cyproterone; Dexamethasone; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypothalamus; Infant; Insulin; Metyrapone; Nephrotic Syndrome; Obesity; Pituitary Gland; Prednisone; Vasopressins

Topics: Acidosis; Acute Kidney Injury; Alkalosis; Amyloidosis; Hodgkin Disease; Humans; Hyperkalemia; Hypernatremia; Hypertension, Renal; Hypokalemia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Multiple Myeloma; Neoplasms; Nephritis; Nephrotic Syndrome; Osmolar Concentration; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Acute Kidney Injury; Animals; Blood; Cardiac Glycosides; Dehydration; Diuretics; Glomerular Filtration Rate; Heart Failure; Hyponatremia; Kidney Failure, Chronic; Liver Cirrhosis; Mineralocorticoid Receptor Antagonists; Nephrotic Syndrome; Sodium; Syndrome; Vasopressins; Water

Topics: Acute Kidney Injury; Glomerulonephritis; Humans; Hypertension, Renal; Kidney Diseases; Kidney Failure, Chronic; Kidney Transplantation; Kidneys, Artificial; Nephrotic Syndrome; Pyelonephritis; Transplantation, Homologous; Vasopressins

Nephrotic syndrome is characterized by water and sodium retention, which leads to edema formation. The nonosmotic stimulation of arginine vasopressin (AVP) release from the pituitary gland has been implicated to be one of the important factors of abnormal water retention in patients with nephrotic syndrome. It is not known, however, whether nephrotic syndrome is associated with stimulation of hypothalamic vasopressin gene expression. Puromycin aminonucleoside is known to cause altered glomerular permeability, which results in experimental nephrotic syndrome in rats. In the present study, therefore, AVP gene expression has been studied in the hypothalamus of rats with puromycin aminonucleoside-induced nephrotic syndrome (PNS). Nephrotic syndrome was induced by a single intravenous injection of puromycin aminonucleoside (50 mg/kg body weight). Nephrotic syndrome was confirmed by urinary protein excretion (control 20.8 +/- 3.5 mg/24 hr v PNS 273.9 +/- 41.4 mg/24 hr; P < 0.0001, n = 6) and serum albumin concentrations (control 4.52 +/- 0.07 g/dL v PNS 2.96 +/- 0.22 g/dL; P < 0.001, n = 6). In PNS rats, plasma AVP was significantly higher than in control rats (control 0.77 +/- 0.10 pg/mL v PNS 2.13 +/- 0.42 pg/mL; P < 0.005, n = 12), even though there were no differences in plasma osmolality (control 292.0 +/- 2.0 mOsm/kg H2O v PNS 290.3 +/- 2.5 mOsm/kg H2O; P = NS, n = 12) or serum sodium concentration (control 142.7 +/- 0.7 v PNS 142.1 +/- 1.1; PNS, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Gene Expression; Hypothalamus; Male; Nephrotic Syndrome; Puromycin Aminonucleoside; Rats; Rats, Sprague-Dawley; RNA, Messenger; Vasopressins

We explored the role of angiotensin II and vasopressin in the maintenance of blood pressure during the nephrotic syndrome of adriamycin-induced nephropathy in rats. All 91 rats treated with adriamycin developed chronic renal failure with nephrotic syndrome, which was more pronounced in the normotensive rats than the 35% who became hypertensive. Angiotensin II blockade with DuP 753 produced a significantly greater hypotensive response in both the adriamycin-hypertensive (-16 +/- 3 mm Hg) and adriamycin-normotensive (-14 +/- 5 mm Hg) groups than the saline-treated controls (-5 +/- 1 mm Hg, P < .05). Vasopressin blockade with either a V1V2 inhibitor or a selective V1 inhibitor produced a hypotensive response in adriamycin-hypertensive rats only (by -16 +/- 4 and -17 +/- 2 mm Hg, respectively, P < .01), although the nonselective vasopressin inhibitor produced similar fluid loss and body weight reduction in all three groups. The data suggest that in adriamycin-induced nephropathy with nephrotic syndrome, angiotensin II contributes to blood pressure maintenance in both hypertensive and normotensive animals, whereas the pressor action of vasopressin contributes to elevated blood pressure in hypertensive animals only.

Topics: Angiotensin II; Animals; Biphenyl Compounds; Blood Pressure; Cholesterol; Creatinine; Doxorubicin; Hypertension; Imidazoles; Kidney; Kidney Failure, Chronic; Losartan; Male; Nephrotic Syndrome; Potassium; Rats; Rats, Wistar; Serum Albumin; Sodium; Tetrazoles; Time Factors; Urea; Vasopressins

In accordance with the results of examining 40 children with nephrotic and mixed glomerulonephritis, it has been established that in the pathogenesis of the nephrotic syndrome of paramount importance is imbalance of the output of renal prostanoids, manifesting in the predominance of the vasopressor and proaggregate fraction--thromboxane A2 and in the deficiency of its antagonist prostacyclin that exerts a protective action on glomerular filtration. Sodium and water retention in patients with the nephrotic syndrome favours an increase of the content of antidiuretic hormone and plasma renin activity.

Topics: 6-Ketoprostaglandin F1 alpha; Child; Circadian Rhythm; Dinoprost; Dinoprostone; Humans; Nephrotic Syndrome; Renin-Angiotensin System; Thromboxane B2; Vasopressins; Water-Electrolyte Balance

Prostanoid excretion with urine in children suffering from glomerulonephritis indicates that in the kidneys the output of prostacycline decreases and that of thromboxan rises. In glomerulonephritis children prostacycline and prostaglandin E promote the maintenance of glomerular filtration, which is evidenced by the reduction of their output in the stage of chronic renal failure. The growth of renin and antidiuretic hormone synthesis in children suffering from nephrotic glomerulonephritis is not accompanied by the increase of the output of prostaglandin E, their renal antagonist, and may be one of the reasons of the development of the edematous syndrome.

Topics: Adolescent; Child; Child, Preschool; Diet, Sodium-Restricted; Glomerulonephritis; Humans; Kidney; Nephrotic Syndrome; Prostaglandins; Renin; Vasopressins

Changes in blood plasma content of hormones which are observed in the different periods of hemorrhagic fever and the attendant renal syndrome are directed to the maintenance of significantly deranged water-electrolyte homeostasis. Adequate secretion of vasopressin and aldosterone in response to the changes in sodium concentration and plasma osmolality point to the absence of significant functional disorders of the corresponding glands. Pronounced hypernatremia in fatal cases is evidence of the deranged processes of osmoregulation associated primarily with kidney areactivity to vasopressin and prognostically is an unfavourable sign. The presence of pituitary necrosis in deceased subjects does not rule out the role of vasopressin deficiency in the pathogenesis of pronounced hypernatremia.

Topics: Acute Kidney Injury; Adolescent; Adult; Aldosterone; Female; Hemorrhagic Fever with Renal Syndrome; Humans; Hypernatremia; Hyponatremia; Male; Middle Aged; Nephrotic Syndrome; Osmotic Pressure; Renin; Vasopressins

Topics: Child; Child, Preschool; Diuresis; Glomerulonephritis; Humans; Immersion; Kidney; Nephrotic Syndrome; Time Factors; Vasopressins

The roles of the antidiuretic hormone arginine-vasopressin (AVP), atrial natriuretic peptide (ANP), renin, aldosterone and catecholamines in the pathogenesis of impaired water excretion were studied in edematous children with nephrotic syndrome. Compared to non-proteinuric children with nephrotic syndrome in remission, edematous children during relapse had lower serum concentrations of sodium and chloride with lower plasma osmolality, but had higher hematocrit values (P less than 0.05, each). Plasma concentration of AVP was higher in edematous children (P less than 0.01). Compared to healthy, normal children, edematous nephrotic children had higher plasma concentrations of AVP, aldosterone, renin, noradrenaline, and adrenaline (P less than 0.01, each), but had similar levels of plasma ANP. Head out water immersion and infusion of 5 ml/kg 20% human serum albumin solution, both procedures known to increase central blood volume, resulted in a reduction of elevated hormone concentrations to near-normal levels and caused a rise in sodium and water excretion. Following albumin infusion, mean ANP rose fivefold, and plasma concentrations of this hormone correlated positively with urine flow (r = 0.64, N = 18, P less than 0.01) and with sodium excretion (r = 0.62, N = 18, P less than 0.01). It is concluded that AVP, renin, aldosterone and catecholamines are stimulated in edematous children with nephrotic syndrome by reduction in effective circulatory blood volume. Central blood volume expansion induced either by water immersion or by infusion of concentrated albumin solution is able to correct elevated hormone levels and to induce salt and water excretion. Plasma ANP appears to trigger the diuretic and natriuretic effects of central volume expansion.

Topics: Aldosterone; Blood Proteins; Body Water; Catecholamines; Child; Diuresis; Hematocrit; Humans; Immersion; Kidney Function Tests; Nephrotic Syndrome; Renin; Vasopressins

Topics: Adolescent; Aldosterone; Child; Child, Preschool; Female; Humans; Immersion; Kidney Function Tests; Male; Nephrotic Syndrome; Norepinephrine; Renin; Renin-Angiotensin System; Vasopressins

Decreased free water excretion and the development of interstitial edema are recognized characteristics of preeclampsia. However, the pathophysiology of decreased urine excretion in preeclampsia is presently controversial: diminished glomerular filtration, renal arteriolar spasm, elevated plasma vasopressin levels, and plasma volume contraction have been suggested as etiologies. We studied seven pregnant patients with a diagnosis of mild preeclampsia to assess the role of vasopressin, serum protein, and glomerular function in the renal excretion of water. The ability to excrete a water load was significantly and directly correlated with serum albumin (P less than 0.05) and protein (P less than 0.02) concentrations. Neither plasma vasopressin nor creatinine clearance correlated with water excretion. The similarity of preeclampsia and the nephrotic syndrome with regard to the renal excretion of water is discussed.

Topics: Anuria; Edema; Female; Glomerular Filtration Rate; Humans; Nephrotic Syndrome; Oliguria; Pre-Eclampsia; Pregnancy; Vasopressins; Water

To verify whether or not an increased secretion of ADH may cause the water retention commonly observed in nephrotic syndrome, 16 nephrotic patients and 13 normal control subjects were studied in basal conditions and following a water load or an iso-osmotic blood volume expansion by 20% albumin infusion. In the basal condition there were no differences in plasma ADH, urine output, urinary osmolality (UOsm), and plasma renin activity between nephrotic patients and control subjects; POsm, PNa+, UNaV, and blood volume (BV) instead, were significantly lower in nephrotic patients than in control subjects. Following the water load control subjects reached a minimal UOsm of 82 +/- 12 mOsm/kg at 60 min and excreted completely the ingested water in 150 min; nephrotic patients reached a minimal UOsm of 160 +/- 111 mOsm/kg at 120 min, and the water was eliminated completely in 240 min. Plasma ADH decreased significantly in the first hour following water load only in control subjects. A significant direct correlation was observed between plasma ADH and POsm in control subjects (ADH = -85 + 0.30 POsm, P less than 0.001) but not in nephrotic patients. Plasma ADH was inversely correlated with BV in nephrotic patients (ADH = 15.47 -0.17 BV, P less than 0.001) but not in normal control subjects. In nephrotic patients with reduced BV the expansion of BV with 20% albumin was effective in reducing the plasma levels of ADH and promoting a water diuresis. Our results demonstrate a sustained volume mediated secretion of ADH in the nephrotic syndrome, which is responsible for the impairment in water excretion.

Topics: Adolescent; Adult; Blood Volume; Child; Female; Glomerulonephritis; Hematuria; Humans; Male; Middle Aged; Nephrotic Syndrome; Osmolar Concentration; Vasopressins; Water-Electrolyte Imbalance

In order to verify whether or not an increased secretion of ADH may cause the water retention commonly observed in nephrotic syndrome, 12 nephrotic patients and 11 normal subjects were studied in basal conditions and following a water load or iso-osmotic blood volume expansion. A significant direct correlation was observed between plasma ADH and Posm in controls but not in nephrotics. Plasma ADH was inversely correlated with BV in nephrotics but not in controls. Blood volume expansion in nephrotic patients was effective in reducing plasma ADH and promoting a water diuresis. These results demonstrate a sustained volume mediated secretion of ADH in nephrotic syndrome, which is responsible for the impairment in water excretion.

Topics: Blood Volume; Diuresis; Humans; Nephrotic Syndrome; Vasopressins

Topics: Blood Volume; Female; Humans; Hypercalcemia; Kidney Diseases; Lupus Erythematosus, Systemic; Nephrotic Syndrome; Potassium Deficiency; Retroperitoneal Fibrosis; Urogenital Neoplasms; Vasopressins

Topics: Adolescent; Adult; Chromium; Diuresis; Female; Glomerulonephritis; Humans; Hypertension; Kidney; Kidney Diseases; Kidney Function Tests; Male; Mannitol; Middle Aged; Nephrotic Syndrome; Pyelonephritis; Vasopressins

Topics: Adolescent; Adrenal Glands; Adrenal Insufficiency; Adrenocorticotropic Hormone; Child; Child, Preschool; Depression, Chemical; Female; Humans; Hydrocortisone; Infant; Male; Nephrotic Syndrome; Prednisone; Spectrometry, Fluorescence; Stimulation, Chemical; Time Factors; Vasopressins

Topics: Adrenal Cortex Hormones; Aldosterone; Anti-Inflammatory Agents; Antigen-Antibody Reactions; Basement Membrane; Cell Membrane Permeability; Female; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Kidney; Kidney Glomerulus; Male; Mineralocorticoids; Nephrotic Syndrome; Vasopressins

Topics: Aldosterone; Feedback; Humans; Nephrotic Syndrome; Vasopressins; Water-Electrolyte Balance

Topics: Age Factors; Aldosterone; Animals; Bibliographies as Topic; Carbohydrate Metabolism; Cyclic AMP; Germany, East; Glucocorticoids; History of Medicine; Kidney; Nephrotic Syndrome; Permeability; Rats; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Biological Assay; Eclampsia; Edema; Female; Heart Failure; Humans; Male; Methods; Nephrotic Syndrome; Pregnancy; Rats; Vasopressins

Topics: Adolescent; Adult; Aged; Edema; Female; Heart Failure; Humans; Male; Middle Aged; Nephrotic Syndrome; Pregnancy; Vasopressins

Topics: Arginine Vasopressin; Humans; Kidney Diseases; Nephrotic Syndrome; Vasopressins

Topics: Adrenocorticotropic Hormone; Albumins; Child; Humans; Kidney Glomerulus; Nephrosis; Nephrotic Syndrome; Permeability; Vasopressins