Acute Water Load Research Articles

Inter-relationship between urinary kallikrein-kinins and arginine vasopressin in man.

1. Physiological saline solution was infused in nine normal subjects and six patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected intramuscularly. Urine was collected in 30 min fractions before and after AVP administration. 2. The urinary excretions of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) and immunoreactive kinins (i-kinins) were significantly lower in patients with DI than in normal subjects before AVP administration, while there were no differences in plasma renin activity, plasma aldosterone concentration, creatinine clearance and blood pressure between the two groups, except for a marked water diuresis in patients with DI. The urinary excretion of KAL-A and i-kinins correlated positively with the urinary excretion of AVP. 3. AVP administration increased both plasma AVP and urinary excretion of AVP to similar levels in both groups. As a result, urine volume decreased to a greater degree in patients with DI than in normal subjects. In contrast, the urinary excretions of KAL-A and i-kinins were increased by AVP administration, with a greater response in normal subjects than in the patients with DI. 4. After overnight fasting, acute water loading was carried out orally for 15 min in six normal subjects. At 30 min plasma AVP was suppressed by water loading to almost the basal level found in patients with DI. Urinary excretions of KAL-A and i-kinins in the first 30 min fraction after loading were also suppressed to the basal level in patients with DI. Later, the urinary excretion of KAL-A increased together with the increase in urine flow. Urine volume and free water clearance markedly increased except in the first 30 min fraction, compared with the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

Interrelationship between urinary kallikrein and arginine-vasopressin in man.

Physiological saline solution was infused in 9 normal subjects and 6 patients with central diabetes insipidus (DI). At 120 min after the start of infusion, arginine vasopressin (AVP) was injected (i.m.). Urine was collected every 30 min fraction. The urinary excretion of kallikrein-like activity (KAL-A) (S-2266 hydrolysis activity) was significantly lower in patients with DI than in normal subjects, without showing the differences of plasma renin activity (PRA), plasma aldosterone concentration (PAC), creatinine clearance (Ccr) and blood pressure between the two groups, except a marked water-diuresis in DI. The urinary excretion of KAL-A correlated positively with the urinary excretion of AVP. AVP administration significantly increased the urinary excretion of KAL-A. After overnight fasting, an acute oral water-loading was carried out for 15 min in 6 normal subjects. Concomitant with a significant suppression of the level of plasma AVP from the first 30 min, a slight, but significant, decrease in urinary excretion of KAL-A was observed in the first 30 min fraction after loading, compared with the control period. Afterwards, the urinary excretion of KAL-A increased prominently with an increase in urine flow. KAL-A in the urine decreased promptly from the first 30 min fraction and then gradually until 120 min after loading. Urine volume and free-water markedly increased except the first 30 min fraction, compared with the control period. Thus it is suggested that AVP is one of factors which actually regulate the secretion of renal kallikrein in man.

Single kidney function: Effect of acute protein and water loading on microalbuminuria

The hyperfiltration induced by an acute response to an oral protein and water load was investigated to ascertain whether it can modify the urinary albumin excretion (UAE) in the microalbuminuric range by further increasing the glomerular filter permeability. To this end, six patients with a single kidney selected as having microalbuminuria on a regular diet without the clinical or laboratory data of overt renal disease and eight healthy subjects received a short-term protein and water load (150 g of meat-derived protein and 1 liter of water). In patients with one kidney, mean basal UAE values were significantly higher than in control subjects (p <0.006), whereas endogenous creatinine clearance values were only slightly lower (p >0.05). One hour after the protein and water load, an abrupt increase in microalbuminuria levels was found in patients with one kidney and mean UAE values were significantly higher than in control subjects (p <0.002), whereas mean creatinine clearance values were significantly lower in patients than in control subjects (p <0.01). High UAE (p <0.002) and low creatinine clearance (p <0.002) values were maintained over the following four hours in patients with one kidney. These data suggest that in the single kidney with reduced renal functional reserve, an oral protein and water load magnifies the pre-existing loss of glomerular permselective properties due to chronic hyperfiltration as manifested by a further increase in microalbuminuria.

Single kidney function: Effect of acute protein and water loading on microalbuminuria

Single kidney function: Effect of acute protein and water loading on microalbuminuria

Increased PGE2 excretion by dDAVP in humans depends on state of hydration.

The relationship of renal prostaglandin E2 (PGE2) excretion (UPGEV) to water deprivation, water diuresis, and subsequent antidiuresis by 1-desamino-8-D-arginine vasopressin (dDAVP) was studied in female volunteers. After 16 h of water deprivation, the subjects began a sustained water diuresis for 8 h. This diuresis caused a transient twofold rise in UPGEV at 2 h (P less than 0.05), which then fell back to or below baseline levels. dDAVP given during the water diuresis caused a transient rise of UPGEV as urine volume decreased and plasma osmolality fell from 277 +/- 1.5 to 271 +/- 2 mosmol/kg (P less than 0.01). Another group of subjects had the water diuresis discontinued after 4 h with dDAVP given at the 5th h when urine volume was decreasing and urine osmolality was increasing. In this setting dDAVP did not produce as great a fall in plasma osmolality nor did it increase UPGEV. These data indicate that renal prostaglandin synthesis (as determined by UPGEV) is increased transiently by an acute water load; dDAVP given during continued water ingestion results in a fall in plasma osmolality and increased PGE excretion; however, dDAVP does not increase UPGEV during normal hydration; and UPGEV is independent of changes in urine flow. These findings imply that renal prostaglandins may have a functional role in humans to inhibit the hydroosmotic actions of antidiuretic hormone, and thus hasten the excretion of a water load, and to prevent overhydration when inappropriate antidiuresis occurs. However, there is no evidence that the stimulus for prostaglandin production is dDAVP per se.

Effects of acute water load, hypertonic saline infusion, and furosemide administration on atrial natriuretic peptide and vasopressin release in humans.

A new specific RIA for alpha-human atrial natriuretic hormone (alpha hANP) was used to determine whether changes in plasma volume elicited by acute water loading, hypertonic saline infusion, and furosemide administration caused changes in ANP release and resultant changes in renal and cardiovascular function in normal subjects. In addition, changes in plasma arginine vasopressin (AVP), PRA, and aldosterone concentrations were studied simultaneously. Mean plasma alpha hANP and AVP levels were 51.3 +/- 16.0 (+/- SE) and 3.1 +/- 0.6 pg/ml, respectively, in the basal state. Plasma alpha hANP rose to 77.8 +/- 27.6 in response to a 4.5% increase in plasma volume induced by water loading, increased further to 134.1 +/- 28.9 in response to a 23% volume increase induced by hypertonic saline, and fell to 70.2 +/- 15.8 pg/ml in response to a decrease in plasma volume after furosemide treatment (P less than 0.01-0.05). On the other hand, plasma AVP fell to 1.8 +/- 0.1 pg/ml after the water load, rose to 4.1 +/- 0.6 after hypertonic saline, and rose further to 5.8 +/- 0.8 pg/ml after furosemide (P less than 0.01-0.05). Water and hypertonic saline loading decreased PRA, but plasma aldosterone concentrations did not change; subsequent furosemide administration increased both (P less than 0.01-0.05). Arterial pressure and heart rate did not change significantly. Increases in urinary Na excretion and osmolar clearances were associated with a rise in plasma alpha hANP after water loading and hypertonic saline infusion (P less than 0.01-0.05), but changes in urine flow were mainly associated with alterations in AVP release. associated with alterations in AVP release.

Renal function in sea snakes. I. Glomerular filtration rate and water handling.

Renal clearance studies were performed on anesthetized sea snakes (Aipysurus laevis) under various salt and volume loads. The median values for the control glomerular filtration rate (GFR) and urine flow rate (V) were 0.78 and 0.11 ml X kg-1 X h-1, respectively. Acute salt loading with 1 mol/l NaCl significantly increased V to 0.68 ml X kg-1 X h-1, whereas acute water loading significantly decreased GFR to 0.17 ml X kg-1 X h-1. Acute loading with either isosmotic NaCl or seawater did not significantly alter either V or GFR. Chronic loading with water or seawater by intraperitoneal injection significantly increased both GFR and V. No consistent relationship between plasma osmolality and GFR was observed. Instead a threshold-type relationship existed between GFR and plasma K concentration. Within each treatment group, high plasma K concentrations were correlated with low GFRs. There was an abrupt increase in GFR at low plasma K concentrations, the inflection point ranging from 2.5 to 4 mmol/l K depending on the experimental treatment. A curvilinear relationship existed between V and GFR; as GFR increased, V approached a maximal limiting value. At low GFRs (less than 0.2 ml X kg-1 X h-1), V often exceeded GFR, indicating net fluid secretion that was correlated with net Na movement. In addition, there was an inverse relationship between urine-to-plasma osmolality ratio and V. At low values of V, urine osmolalities modestly exceeded those of the plasma. Overall, renal function of A. laevis appears to be adapted to conserve water.

The syndrome of self-induced water intoxication in psychiatric patients.

This is a report on six psychiatric patients who indulged in excessive ingestion of water and subsequently developed tonic-clonic seizures in the course of the underlying mental disorders. On the basis of the DSM-III criteria, they were diagnosed as follows: schizophrenic disorder, 4; schizo-affective disorder, 1; borderline personality disorder, 1. The levels of serum electrolytes were estimated during five episodes of seizures in three patients. Hyponatremia was a consistent finding (serum sodium: mean = 120.6 mEq/liter). Plasma osmolality and plasma levels of arginine vasopressin (AVP) were determined during two episodes in two patients. The inappropriately high circulating levels of AVP relative to plasma hypoosmolality were documented. However, the response to the overnight fluid deprivation and acute water load during the period of no seizures in two patients revealed no evidence of the persistent SIADH, suggesting the temporal association of hyponatremic encephalopathy with inappropriate AVP secretion. It is not conclusive whether the transient SIADH is the cause or the consequence of hyponatremic encephalopathy, although a delusion or an auditory hallucination could play a critical role in drinking water excessively in three patients.

Mechanism of Action of Indomethacin in Tubular Defects

Indomethacin, a potent prostaglandin synthesis inhibitor, has been proven to be effective in a number of tubular defects characterized by enhanced prostaglandin (namely, prostaglandin E2 (PGE2) production, but its mechanism of action is poorly understood. To elucidate further the mechanism(s) by which indomethacin reverses the abnormal tubular functions, five children with different tubular defects (nephrogenic diabetes insipidus, three cases; Fanconi syndrome, one case; and pseudohypoaldosteronism, one case) were treated with indomethacin. Indomethacin, 1 mg/kg every eight hours, was given for 1 week to all children and then was given chronically to four of the children who responded to the drug. Its use was suspended in a 10 year-old-boy with nephrogenic diabetes insipidus because it proved ineffective. To assess the site along the nephron where indomethacin affects the solute and water excretion, an acute water load study was performed in three responsive children before and during the treatment. Indomethacin did not significantly alter the glomerular filtration rate but was effective in reducing diuresis and levels of urinary sodium and potassium excretion. In the child with Fanconi syndrome, indomethacin was also effective in controlling the urinary loss of phosphate, urate, glucose, and bicarbonate. Results of the water load studies show that indomethacin decreases the delivery of solute from the proximal tubule, reduces the fractional free water clearance, and increases the urine-plasma osmolar ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on Prediction of Hypertension in Spontaneously Hypertensive Rats (SHR)

Urinary Na excretion following acute peroral water loading was clearly increased in SHRSP and SHR compared with WKY even at the age of 4 weeks before the development of hypertension. Cold exposure before and after adrenal denervation did not affect such water-induced exaggerated natriuresis which, therefore, might possibly be involved in genetic mechanism or disposition to hypertension. Since these hypertensive models are prone to retain Na intracellularly (Yamori: In Hypertension; Physiopathology and Treatment: 556-581, 1983), acute water loading may enhance urinary Na excretion. This phenomenon observed even in prehypertensive stage can be utilized as a predictor for hypertension in SHR and SHRSP and possibly for essential hypertension in men.

Urinary kallikrein response to acute saline or water loads in hypertensive and normal humans.

Urinary kallikrein excretion during acute water or saline loading was studied in normal and hypertensive humans after chronic Na+ depletion and Na+ loading to answer the following questions. 1. Is urinary kallikrein a natriuretic or diuretic substance? 2. During acute water or saline loading, does the underlying Na+ balance influence (a) the urinary kallikrein response? or (b) the relationship between urinary kallikrein and renal Na+ or water handling? 1) Urinary kallikrein did not change during a 1.2 liter water load given to nine white hypertensive and five white normal men. Urinary kallikrein was significantly decreased, however, in five white hypertensive and five white normal subjects during and after 1 hour of isotonic saline infusion (30 ml/kg). In sodium-depleted hypertensive patients kallikrein excretion was decreased from 19.8 to 9.5 mEU /min, and in Na+-depleted normal subjects it was decreased from 15.7 to 12.6 mEU /min (p = 0.003). The response in hypertensive patients was not different from normal subjects. In all Na+-loaded subjects, kallikrein excretion was also significantly decreased during isotonic saline infusion (p = 0.01). Urinary kallikrein did not change in three other subjects given hypertonic saline. 2(a) The underlying state of Na+ balance influenced the baseline level of kallikrein excretion, but not the directional decline in kallikrein during isotonic saline. (b) In Na+-restricted hypertensives given isotonic saline, urinary kallikrein was inversely related to the fractional excretion of Na+ (r = -0.54, p less than 0.01) and the tubular reabsorption of H2O (TcH2O/GFR; r = -0.50, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of postural changes on ADH release and the renal handling of sodium and water in patient with idiopathic edema.

In order to investigate the role of ADH and the renal handling of sodium and water in patients with idiopathic edema, 21 patients were subjected to acute oral water load tests. Although a normal water diuresis was observed in al patients in supine posture, it was markedly impaired in upright posture with significant decreases in sodium, free water, and osmolar clearances. In particular, two patients exhibited the continuous production of concentrated urine after the water load in upright posture. The fractional reabsorption of sodium at the proximal tubules was significantly increased in upright posture, while the glomerular filtration rate did not change significantly. The constricting of both legs with elastic bandages tended to improve the water diuresis in upright posture, suggesting that the pooling of blood into the lower legs might be contributing to the formation of idiopathic edema. The patients showed normal osmoregulation of ADH release in supine, but not in upright posture: the suppression of ADH release in upright posture was only transient or incomplete despite a sufficient fall in plasma osmolality following the water load. Thus, both an increase in renal sodium reabsorption and the insufficient suppression of ADH release in upright posture might contribute to the retention of body fluid in patients with idiopathic edema.

Effects of fluid intake on basal and vasopressin-responsive urinary prostaglandin E.

The effects of fluid intake on basal and vasopressin-responsive urinary PGE excretion (UPGEV) were examined in conscious rats under conditions of 1) ad libitum water intake, 2) water deprivation, and 3) water diuresis induced by ad libitum intake of 5% dextrose in water. UPGEV fell progressively during 40 h of water deprivation. Water diuresis after water deprivation increased UPGEV transiently (8 h). Vasopressin (Pitressin tannate in oil, 5 U/kg subcutaneously) increased UPGEV and decreased urine volume (V) in rats on ad libitum water intake but did not alter UPGEV during water deprivation. Indomethacin suppressed UPGEV (70-90%), increased basal urine osmolality (Uosmol), and potentiated the antidiuretic response to Pitressin in rats on ad libitum water intake. Indomethacin accelerated by 8 h the onset of maximal antidiuresis in water-deprived rats but did not significantly alter water balance. During water diuresis, UPGEV declined in the first 8 h after Pitressin. Thereafter, UPGEV increased markedly, concurrent with early vasopressin escape. Indomethacin or meclofenamate inhibited the rise in UPGEV, the decline in Uosmol, and the increase in V of the escape phase. Indomethacin or meclofenamate also impaired the excretion of an acute water load (5% body wt) given during escape. The spontaneous decline in UPGEV during hydropenia may serve to maximize physiologic antidiuresis. Conversely, the marked increase in UPGEV induced by administration of vasopressin during water diuresis may serve to suppress the antidiuretic response and thus play a role in the mediation of escape from physiologically inappropriate antidiuresis.

Vascular Effects of Arginine-Vasopressin, Angiotensin and Noradrenaline in Adrenal Insufficiency

Publisher Summary Non-osmotic release of arginine-vasopressin (AVP) is present in conscious, adrenalectomized animals with either gluco- or mineralocorticoid deficiency. This chapter investigates whether the non-osmotic release of AVP has a vascular effect in the gluco- or mineralocorticoid-deficient state. Administration of a specific inhibitor of the hydroosmotic effect of AVP profoundly improves the capacity of mineralocorticoid- or glucocorticoid-deficient animals to excrete an acute water load. Using a sensitive and potent AVP vascular antagonist, a vascular role of endogenous AVP to maintain mean arterial pressure is observed in adrenal insufficiency in the conscious rat. The effect is more readily demonstrable in the mineralocorticoid- than the glucocorticoid-deficient state. Activation of the renin-angiotensin and sympathetic nervous systems in the mineralocorticoid deficient state also contributes to the maintenance of blood pressure. In the mineralocorticoid-deficient state, antagonism of the renin-angiotensin system or α-adrenergic blockade is associated with prolongation of the hypotensive effect of the AVP vascular antagonist. Thus, AVP, angiotensin II, and adrenergic stimulation all combine to support mean arterial pressure in the mineralocorticoid-deficient, conscious rat.

Potential role of increased sympathetic activity in impaired sodium and water excretion in cirrhosis.

In a study of 26 patients with cirrhosis, plasma norepinephrine concentrations were significantly higher in 19 patients who abnormally excreted an acute water load than in seven who excreted the load normally (8324 +/- 116 vs. 306 +/- 33 pg per milliliter; P less than 0.001). There was also a significant positive correlation between plasma levels of norepinephrine and arginine vasopressin after the water load, as well as a negative correlation between plasma norepinephrine and the percentage of the load excreted. A positive correlation between plasma norepinephrine and plasma renin activity, as well as between norepinephrine and aldosterone, was observed. In addition, there was a negative correlation between plasma norepinephrine and urinary sodium excretion. These findings indicate that increased sympathetic activity, as assessed by plasma levels of norepinephrine, correlates closely with sodium and water retention in cirrhotic patients and thus may be of pathogenetic importance.

Role of extracellular volume expansion in the development of DOC-salt hypertension in the rat.

Changes in inulin space, plasma and blood volume, exchangeable and "noninulin" sodium were studied during the prehypertensive, early and late hypertensive stages of deoxycorticosterone (DOC)-salt administration in the rat. The effect of an acute water load in previously nephrectomized animals was also studied. Hypertension developed after 1 to 2 weeks of the DOC-salt regimen and was always preceded by enlargement of the inulin space and increased plasma and blood volume. Expansion of extracellular fluids receded when blood pressure started to rise but reappeared after 4 to 6 weeks of treatment. Plasma sodium was high only in the hypertensive groups. An acute water load increased blood pressure of normal rats and decreased blood pressure of DOC-salt early hypertensive rats. These findings suggest that extracellular volume expansion inhibits a vasopressor mechanism that involves vasopressin and could be stimulated by hypernatremia.

Urinary excretion of albumin in normal man: The effect of water loading

The urinary excretion of albumin and beta 2-microglobulin in response to two different types of oral water load was studied in 18 healthy subjects. Both acute water loading (1 litre of tap water given over 10 min) and chronic water loading (250 ml of water given every 20 min for the 4-h duration of the test) produced a short-lived but significant increase in the urinary excretion of albumin, but not in beta 2-microglobulin. Albumin excretion returned promptly to basal values in spite of high and sustained urine flow. The decrease in haematocrit, plasma osmolality, plasma sodium concentration and pulse rate and the increase in creatinine clearance suggest that the elevation in albumin excretion might be the result of a transient volume expansion associated with an increase in glomerular filtration rate and in filtration of albumin. However, a washout of proteins from the tubular lumen with preferential reabsorption of small molecular weight proteins (i.e. beta 2-microglobulin) during high tubular flow cannot be excluded. Studies investigating changes in urinary albumin excretion should be performed after baseline conditions of stable urinary excretion of albumin have been established.

Role of vasopressin in the impaired water excretion of glucocorticoid deficiency

The mechanism whereby glucocorticoid deficiency impairs renal water excretion was studied in the conscious mineralocorticoid-replaced, adrenalectomized rat. Control animals received physiologic replacement with prednisolone, and experimental animals were deprived of glucocorticoid hormone for either 1 or 14 days. The control animals excreted 95 +/- 1.9% of an acute water load (30 ml/kg) in 3 hours, a value significantly higher than the volume excreted by animals deprived fo glucocorticoid hormone for 1 day (70.0 +/- 3.6%, P less than 0.01) and 14 days (40.0 +/- 3.9%, P less than 0.01). Following the acute water load, plasma vasopressin levels, as measured by radioimmunoassay, was 1.08 pg/ml in the control rats, a value significantly lower than values obtained after the water load in rats deprived of glucocorticoid hormone for 1 day (2.5 +/- 0.2 pg/ml, P less than 0.01) and 14 days (2.4 +/- 0.3 pg/ml, P less than 0.01). To further examine the effect of plasma vasopressin in the impaired water excretion of glucocorticoid deficiency, we performed studied in Brattleboro rats with central diabetes insipidus. In these animals with absence of vasopressin, a defect in water excretion was observed after 14 days, but no 1 day, of glucocorticoid deficiency. In Sprague-Dawley rats, the impaired water excretion after 14 days of glucocorticoid deficiency was associated with a significantly lower cardiac index (209 +/- 14 vs. 291 +/- 11 ml/min/kg, P less than 0.01) and renal blood flow (3.8 +/- 0.3 vs. 5.7 +/- 0.2 ml/min/g, P less than 0.01) than that observed after 1 day of glucocorticoid deficiency. In diabetes insipidus rats, after 14 days of glucocorticoid deficiency, the percentage of an acute water load excreted (121 +/- 7% vs. 158.7 +/- 7.0%, P less than 0.01) was lower than that observed after 1 day of glucocorticoid deficiency. In summary, the present results indicate that glucocorticoid deficiency impairs renal water excretion by both vasopressin-dependent and vasopressin-independent mechanisms. The vasopressin-dependent renal mechanism is associated with a marked decrease in both systemic and renal hemodynamics.

Response of Serum Prolactin to Exogenous Stimulation

Previous observations by other workers indicating suppression of serum prolactin (hPRL) by water loading could not be confirmed. Sequential testing using an acute water load in patients with various clinical diagnoses did not aid conclusively in differentiating functional hyperlactinemic states from pituitary adenoma. It was of interest that the acute ingestion of water resulted in a triphasic response in serum hPRL levels. The response to breast stimulation was more marked in patients with excessive breast hypertrophy and galactorrhea. This was in contrast to patients with hypo- or hyperthyroidism, anorexia nervosa, and our normal subjects. In response to breast stimulation, there was no difference among the normal group, women with functional hyperlactinemia, and patients with proven pituitary adenoma. When they were compared with other patient groups in this study, marked responsiveness was found in patients with amenorrhea and galactorrhea, amenorrhea with elevated hPRL levels without galactorrhea, breast hypertrophy, and adrenal overactivity in response to these two stimuli. The physiologic mechanisms resulting in the increase in serum hPRL levels seen in these patients remain unclear at the present time.

Effects of water load on renal glomerular and tubular function in desert quail.

Effects of an acute intravenous water load on glomerular and tubular function were studied in the anesthetized desert quail Lophortyx gambelii. Total-kidney glomerular filtration rate (GFR) and single-nephron glomerular filtration rates (SNGFR) of reptilian-type and mammalian-type nephrons increased by more than 50% compared with the GFR and SNGFRs measured during a control mannitol diuresis. Despite the increase in GFR, urine flow rate was only 56% of that in control mannitol diuresis, free-water clearance (CH2o) remained at 1-2% of GFR, and the animals excreted only about 79% of the water load. More than 99% of the filtered sodium and 93% of the filtered water were reabsorbed during the water load. Possible reasons for the increased GFR and the failure to produce a dilute urine or excrete the water load are discussed.