“Essential” hypernatremia due to ineffective osmotic and intact volume regulation of vasopressin secretion

A physiological explanation for sustained hyperosmolality was sought in a patient with histiocytosis. During 23 days of observation with only sodium intake regulated at 100 mEq daily, elevation (mean 310 mOsm/kg of water) and fluctuation (range 298-323) of the fasting plasma osmolality were recorded. The presence of endogenous vasopressin was indicated by the patient's ability to concentrate the urine to as high as 710 mOsm/kg of water with a creatinine clearance of 84 cc/min, and by dilution of the urine in response to alcohol. The failure of increasing fluid intake to as high as 6.2 liters daily to lower the plasma osmolality indicated that deficient fluid intake was not solely responsible for the elevated plasma osmolality. Hypertonic saline infusion during water diuresis resulted in the excretion of an increased volume of dilute urine. The water diuresis continued despite a rise in plasma osmolality from 287 to 339. An isotonic saline infusion initiated during hydropenia resulted in a water diuresis which continued despite a rise in the plasma osmolality from 303 to 320. Stable water diuresis induced during recumbency by either oral ingestion of water or intravenous infusion of normal saline was terminated by orthostasis and resumed with the return to the recumbent position. Antecedent alcohol ingestion blocked the antidiuresis of orthostasis. The data are interpreted as indicating impairment of the osmoreceptor mechanism as the primary cause of the hyperosmolar syndrome. They also indicate that vasopressin secretion was regulated primarily by changes in effective blood volume. Chlorpropamide was found to be an effective treatment for the syndrome.     

Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs

OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.     

The effect of uncomplicated potassium depletion on urine acidification

Studies were performed on normal human subjects to determine the effects of potassium depletion on urine acidification. Depletion was induced by ingestion of a low potassium diet either alone or in combination with a potassium-binding resin, and the response of each subject to an acute ammonium chloride load in the potassium-depleted state was compared to his normal response. Urine pH was significantly higher during potassium deficiency if sufficient potassium depletion had been induced. No differences in blood acid-base parameters, urinary flow rate, or urinary fixed buffer excretion rate were found to account for this change; however, the increase in urine pH was accompanied by a concomitant increase in net acid and ammonium excretion. It is proposed that these changes during potassium depletion reflect an increase in ammonia diffusion into the urine, presumably as a result of increased renal ammonia production. In addition, it is speculated that changes in ammonia metabolism may be a physiologic control mechanism for potassium conservation.     

Urinary kallikrein and systemic prostacyclin synthesis during sodium chloride infusion in normal man

An intravenous infusion of 3 litres of sodium chloride solution (saline: 150 mmol/l) was given over 1 h to normal subjects. During and immediately after the infusion, renal plasma flow increased in the majority of subjects, but the rise was not statistically significant. Significant increases in urine flow, sodium excretion, urinary kallikrein excretion and urinary excretion of dinor-6-keto prostaglandin (PG) F1 alpha, a measure of systemic PGI2 synthesis, were noted. Plasma renin activity and plasma protein concentration were significantly lowered by the infusion. At 2 h after the end of the infusion, although urine flow fell significantly, sodium excretion had not decreased. The reduction in plasma renin activity and plasma proteins persisted, and excretion of kallikrein and the PGI2 metabolite returned to control values. Overall, urinary kallikrein excretion correlated significantly with urine flow and with sodium excretion. Peak kallikrein excretion occurred in the second 30 min of the infusion, and preceded maximal urine flow and sodium excretion. The results suggest that increased systemic synthesis of PGI2 occurs in response to an acute infusion of sodium chloride, and may be an adaptive response of the vasculature to volume expansion. They support a role for the renal kallikrein-kinin system in the early diuretic and natriuretic response to saline infusion; the reduction in plasma renin activity and plasma protein concentration may be involved in both the early response and the persistent natriuresis 2 h after the infusion.     

Diuresis-dependent excretions of low-molecular mass proteins in urine: beta 2-microglobulin, lysozyme, and ribonuclease

An investigation was carried out into how the low-molecular mass proteins beta 2-microglobulin, lysozyme, and ribonuclease were excreted over 8 h after high fluid intake (22 ml/kg of body weight in 15 min). With increasing urine flow rate the amount of lysozyme excreted per hour or per millimole creatinine increased more markedly than that of beta 2-microglobulin while at the same time the excretion rate of ribonuclease decreased. The effect of urinary flow upon the excretion rates of the various low-molecular mass proteins has to be considered as a preanalytical factor when these proteins are used as indicators of tubular dysfunction.     

Further studies on the mechanism of the natriuretic response to low-dose dopamine in man: effect on lithium clearance and nephrogenic cAMP formation

The effect of intravenous infusion of low-dose dopamine on electrolyte excretion, lithium clearance, nephrogenous cAMP formation and renal haemodynamics was investigated in healthy volunteers. Dopamine significantly increased the urine flow rate by 70.6% and urinary sodium excretion by 72%, but did not change creatinine clearance, PRA or plasma levels of AVP, ANP and cAMP. Renal plasma flow significantly increased by 48.6%; the glomerular filtration rate was not changed. Lithium per se increased basal PRA, but had no effect on the increments of urine flow rate, sodium excretion and renal blood flow induced by dopamine. Dopamine significantly increased the fractional excretion of lithium (representing fractional excretion of sodium at the proximal level). The increase in urinary sodium excretion during dopamine infusion, significantly correlated with the increase in fractional excretion of lithium (r = 0.94; P less than 0.01) and the increase in nephrogenous cAMP formation (r = 0.96; P less than 0.01). No correlation was found between the increase in urinary sodium excretion and the increase in renal blood flow. In conclusion, this study confirms that low-dose dopamine increases renal blood flow and urinary sodium excretion in healthy volunteers. This natriuretic response appears to be due to interaction with proximal tubular dopamine receptors, which are positively coupled to adenylate cyclase.     

Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers.

Prolonged furosemide treatment is associated with urinary loss of thiamine and thiamine deficiency in some patients with congestive heart failure and low dietary thiamine intake. In the rat, diuretic-induced thiamine urinary loss is solely dependent on increased diuresis and is unrelated to the type of diuretic used. We studied the effects of single intravenous doses of furosemide (1, 3, and 10 mg) and of normal saline infusion (750 mL) on urinary thiamine excretion in 6 volunteers. Over a 6-hour period, furosemide induced dose-dependent increases in urine flow and sodium excretion rates (mean +/- SD), from 51 +/- 17 mL/h at baseline to 89 +/- 29 mL/h, 110 +/- 38 mL/h, and 183 +/- 58 mL/h (F = 10.4, P < .002) and from 5.1 +/- 2.3 mmol/h to 9.4 +/- 6.8 mmol/h, 12.1 +/- 2.6 mmol/h, and 20.9 +/- 10.6 mmol/h (F = 6.3, P < .005) for the three doses, respectively (104 +/- 35 mL/h and 13.0 +/- 6.2 mmol/h for the saline infusion). During this period the thiamine excretion rate doubled from baseline levels (mean of four 24-hour periods before the diuretic interventions) of 6.4 +/- 5.1 nmol/h to 11.6 +/- 8.2 nmol/h (F = 5.03, P < .01, for all four interventions, no difference being found between them), then returning over the following 18 hours to 6.1 +/- 3.9 nmol/h. The thiamine excretion rate was correlated with the urine flow rate (r = 0.54, P < .001), with no further effect of the type of intervention or sodium excretion rate. These findings complement our previous results in animals and indicate that sustained diuresis of >100 mL/h induces a nonspecific but significant increase in urinary loss of thiamine in human subjects. Thiamine supplements should be considered in patients undergoing sustained diuresis, when dietary deficiency may be present.     

Urinary pH as a determinant of prostaglandin E2 excretion by the conscious rat

The urinary excretion of prostaglandin E2 (PGE2) was measured in conscious rats under conditions which produced either acid or alkaline urine, but a similar change in fluid and solute excretion. Oral isotonic saline increased both urine flow and sodium excretion but did not alter urinary PGE2 output (which remained constant at 80 pmol/3 h per rat) or urine pH (6.2). When the urine was made alkaline (pH 7.8) by oral sodium bicarbonate or carbonate, urinary PGE2 was approximately 3-fold greater (P less than 0.001) than the control (pH 6.2). The urine flow and sodium output were also increased. When the urine was made acidic (pH 5.7) by oral ammonium chloride, urinary PGE2 excretion was reduced (P less than 0.01) to approximately half the control output. The urine flow and sodium output increased. Within a group of 12 rats receiving oral isotonic saline a positive linear correlation coefficient (P less than 0.002) was established between urine pH and PGE2 excretion. The results indicate that urine pH may be a determinant of PGE2 excretion in unrestrained, conscious rats. It seems likely that this effect of pH is mediated by a change in the passive reabsorption of PGE2 in the distal nephron, although alternative explanations such as altered tubular secretion or synthesis cannot be categorically excluded.     

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.     

The effect of sodium bicarbonate on the flow-dependency of urinary prostaglandin excretion in man

The influence of oral water loading on the excretion rate of prostaglandin (PG) E was investigated in healthy human subjects in a control study where the urine was acidic (pH 5.7) and after oral sodium bicarbonate, which made the urine mildly alkaline (pH 7.2). PGE was immediately extracted from urine and measured by a radioimmunoassay technique. After sodium bicarbonate (5 g) the urinary PGE excretion rate was some three-fold higher (P less than 0.01) than in the control study, in the absence of any significant difference in the urine flow (approximately 80 ml/h). In the control study (urine pH 5.7) the urinary PGE excretion rate increased significantly (P less than 0.01) as the urine flow rose in response to the oral fluid load. However, after sodium bicarbonate, PGE excretion did not alter after the fluid load despite a 10-fold increase in urine flow. Since after bicarbonate administration PGE excretion is independent of urine flow, mildly alkaline urine may represent a condition under which renal PGE synthesis can be effectively assessed from measurements of urinary PGE excretion, in the presence of changes in urine flow. In addition, the results are compatible with the hypothesis that, in man, PGE may be passively reabsorbed in the distal nephron, and a reduction in this reabsorption could contribute to or be responsible for the dependency of the excretion rate of PGE on urine flow.     

Acute effects of high-dose furosemide on residual renal function in CAPD patients.

BACKGROUND: High doses of furosemide can increase urine volume in chronic peritoneal dialysis (CAPD) patients. However, no information is available about effects on urinary solute excretion in relation to residual glomerular filtration rate (GFR), urinary furosemide excretion, and peritoneal solute kinetics. METHODS: Diuretic response and the effect on peritoneal fluid and solute transport parameters were investigated in 7 stable CAPD patients with residual renal function (median urine volume 350 mL/24 hours, range 140- 1900 mL/24 hours). Comparisons were made during two clearance periods of 24 hours: one without (P1) and one during 2 g furosemide (P2). RESULTS: The median increase in urine volume was 400 mL (range 270 - 910 mL, p < 0.02) and the increase in sodium excretion was 54 mmol (range 25 - 118 mmol, p < 0.02). No change in GFR was found between P1 (2.4 mL/ minute, range 0.6 - 5.7 mL/min) and P2 (2.0 mL/min, range 1.0 - 4.8 mL/min). An increase in fractional clearance was found for volume, sodium, potassium, and osmolality (p < 0.02). No change was found in the fractional clearance of urea and electrolyte-free water. Furosemide excretion in urine was 8.7 mg/24 hours (range 2.1 - 38 mg/24 hours) and in dialysate 4.9 mg/24 hours (range 1.9 - 7.8 mg/ 24 hours). Plasma furosemide concentration was 29.5 mg/L (range 6.2 - 43.9 mg/L). A positive correlation was found between residual GFR and total urine furosemide excretion (r = 0.93, p < 0.005). Efficiency, expressed as the increase in fractional sodium clearance (percent) per milligram of furosemide excreted per 24 hours, was 1.2%/mg (range 0.3% - 11.3%/mg). CONCLUSION: High-dose furosemide is effective in CAPD patients in increasing urine volume and electrolyte excretion without affecting urea and creatinine clearance. In CAPD patients, the individual response to an identical high dose of furosemide is dependent on the magnitude of residual GFR.     

Increased urinary excretion of prostaglandin E in patients with idiopathic hypercalciuria

1. Because urinary prostaglandin excretion could play a role in idiopathic hypercalciuria (IH), we studied the excretion of prostaglandin E (PGE), calcium and sodium at various urine flows in 21 patients (14 males) with urolithiasis and IH, seven stone formers (five males) with normal calciuria and 20 controls (11 males). Dietary composition was comparable and sodium intake was restricted to 100-120 mmol/day. 2. Analyses were performed on 30 min urine collections obtained after overnight water deprivation and during water diuresis. Male IH patients had increased levels of urinary PGE at all ranges of urine flow. PGE excretion correlated directly with urine flow in patients and controls, but the slope of this relationship in individual IH male patients was steeper than in controls (P less than 0.01). Calciuria correlated directly with urine output in patients with IH but not in controls. Calcium and sodium excretion were directly correlated (P less than 0.0001) in patients and controls. There were no significant differences between absorptive IH (seven patients) and renal IH (eight patients). There were no significant differences between stone formers with normocalciuria and control subjects. 3. The findings suggest that increased urinary PGE could play a role in the hypercalciuria syndrome, possibly by promoting natriuresis.     

Exaggerated natriuresis in the conscious spontaneously hypertensive rat.

In response to an acute saline load, many patients with essential hypertension exhibit an exaggerated natriuresis relative to normotensive controls. In the present study, the urinary responses of conscious,Okamoto-strain, spontaneously hypertensive rats (SHR), and Wistar-Kyoto strain normotensive rats (NTR) to an acute saline load were evaluated to determine if a similar exaggerated natruiresis exists in this form of hypertension. Twelve rats of each strain per group (12 weeks of age) were housed in metabolism cages for 1 week. Systolic blood pressures (tail cuff) were significantly different (206+/- 9 mm. Hg in SHR and 135 +/- 3 mm. Hg in NTR). After a 4-hour control urine collection, 6 ml. of 0.9 per cent sodium chloride were given by gavage. Urine was collected again for 2 hours. Control urinary excretions of sodium, potassium, and creatinine in SHR and NTR were 11.2 +/- 4.8 muEq per hour, 50.1 +/- 7.6 muEq per hour, and 39.9 +/- 5.5 mg. per hour in SHR, and 13.8 +/- 2.4 muEq per hour, 34.9 +/- 5.5 muEq per hour, and 37.5 +/- 7.1 mg. per hour in NTR, respectively. The respective control values for sodium, potassium, and creatinine excretion in the two groups were not significantly different. Following the saline load, sodium and creatinine excretion rates were significantly elevated in both groups of rats. However, the increase in sodium excretion in SHR (60.8 +/- 7.2 MUEq per hour) was more than double and significantly different from that of the NTR (26.6 +/- 3.7 muEq per hour). In contrast, the increments in creatinine excretion in the two groups of rats were not significantly different from each other. In the NTS, urinary potassium excretion was significantly elevated (59.0 +/- 7.9 muEq per hour) whereas in SHR it was not significantly altered (12.0 +/- 8.8 muEq per hour). The change in urinary creatinine excretion as an index of change in glomerular filtration rate suggests that the greater increase in sodium excretion by the SHR was the result of decreased fractional reabsorption of sodium and not the result of a greater increase in glomerular filtration rate. The exaggerated natriuretic response to salt loading in SHR resembles that in hypertensive man except that in SHR, a simultaneous kaliuretic response is absent.     

Different diuresis-dependent excretions of urinary enzymes: N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase, alkaline phosphatase, and gamma-glutamyltransferase

We studied how much of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) and of the brush-border enzymes alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), and gamma-glutamyltransferase (EC 2.3.2.2) was excreted in urine over 8 h after a high intake of fluid (22 mL per kilogram of body weight). The hourly excretion of all four enzymes increased with the increasing urine flow rate. The excretion rate of the brush-border enzymes was more markedly influenced than that of N-acetyl-beta-D-glucosaminidase. By relating the enzyme excretion to urinary creatinine we could reduce the variability of brush-border enzyme output and could completely compensate for the effect of diuresis on the excretion of N-acetyl-beta-D-glucosaminidase.     

Active and inactive urinary kallikrein in man: effects of diuresis and antidiuresis

1. The urinary excretion of active and inactive kallikrein was studied in volunteers during diuresis induced by water loading or oral frusemide and during antidiuresis induced by desamino-D-arginine-vasopressin. 2. During acute oral water loading, excretion of active kallikrein was unchanged, despite high urine flow rates and low urine osmolalities being achieved. Excretion of inactive kallikrein correlated with the urine flow rate. 3. After desamino-D-arginine-vasopressin in eight water-loaded and six normally hydrated subjects, excretion of inactive kallikrein also correlated with the urine flow rate. There were no significant changes in the excretion of active kallikrein. 4. After frusemide there was a small transient increase in excretion of active kallikrein 1-2 h after dosing which coincided with the maximum diuresis and natriuresis. Excretion of inactive kallikrein again correlated with urine flow rate but the regression relationship between the two variables was different for water-load-induced and frusemide-induced diuresis. 5. These studies do not support a role for urinary kallikrein in the modulation of the antidiuretic action of vasopressin, but suggest that it may contribute to the natriuretic action of frusemide.     

Renal Adaptation to a High Potassium Intake: THE ROLE OF HYDROGEN ION

The influence on urinary acidification of prolonged ingestion of a high potassium diet was explored in normal men and dogs. In men, the response to acute ingestion of ammonium chloride was assessed in a paired fashion after 5 days of ingesting a formula diet of normal or high potassium content; whereas in animals chronically ingesting a small amount of hydrochloric acid, the response to an increase in daily potassium intake was assessed. Urine pH was lower in the potassium-loaded state with both these models, and the effect persisted in the dog studies as long as a high potassium intake was continued. The decrease in urine pH could not be accounted for by changes in plasma acid-base status, net acid excretion, rate of urine flow, urine ionic strength, or fixed buffer excretion, i.e., phosphate, creatinine, or organic acids. Studies of men with administration of exogenous aldosterone and studies of adrenalectomized dogs with constant, maintenance steroid replacement indicated that the decrease in urine pH does not result from altered aldosterone secretion.     

Excretion of digoxin-like immunoreactivity in urine of normal subjects: correlations with excretion of creatinine and electrolytes

To verify whether there is a variation in the 24-h urinary excretion of digoxin-like immunoreactivity (DLIS) in humans, we studied 18 normal adults, who collected their urines for 24-h in several portions. We then measured DLIS (by means of a sensitive RIA method), creatinine, sodium, and potassium concentrations in the urine samples. The mean urinary excretion rate for DLIS in the complete 24-h collection was 84.8 (SD 31.3) pg/min. The mean DLIS urinary excretion rate calculated for overnight collections was significantly lower than those of afternoon collections (P less than 0.01) and the 24-h collection (P less than 0.05). Significant positive correlations were found between urinary DLIS and excretion rates for creatinine (r = 0.347, P = 0.0016), Na+ (r = 0.232, P = 0.038), and K+ (r = 0.323, P = 0.003), respectively. Our data suggest that urinary excretion of DLIS is higher during "active" hours of the day, especially in the afternoon, than at rest, during the night.     

The effects on urinary kinin excretion of oral salt and water loads in dogs

Ten dogs received 1 l of 37 degrees C tap water by stomach tube. Urine flow rate increased from 17 +/- 6 ml in the control hour to 285 +/- 25 ml in the second hour following the water intake. The diuresis was paralleled by increased urine kinin excretion from 23 +/- 9 ng/h to 94 +/- 17 ng/h. Urine kallikrein and urine sodium excretions remained unmodified. In seven dogs urine sodium excretion was increased from 0.87 +/- 0.22 mmol/h to 14.9 +/- 1.9 mmol/h by intragastric administration of 2% NaCl. Urine flow moderately increased from 15.1 +/- 2.5 ml/h to 64.3 +/- 15.0 ml/h. Urine kinin excretion was unchanged. The results suggest a relationship between high rates of urine flow and urinary kinin excretion.     

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)     

Differential effects of atrial natriuretic peptide and dopamine on urinary protein excretion in chronic glomerulonephritis.

1. To examine whether or not atrial natriuretic peptide-induced proteinuria simply results from increases in urine flow or glomerular filtration rate, we infused dopamine (1 microgram min-1 kg-1) and alpha-human atrial natriuretic peptide (0.025 microgram min-1 kg-1) into nine patients with chronic glomerulonephritis and nine essential hypertensive patients without renal damage, and compared the effects of the two agents on renal function and urinary protein excretion. 2. In patients with chronic glomerulonephritis, dopamine infusion significantly increased urinary sodium excretion (+59%), renal blood flow (+20%) and creatinine clearance (+14%). However, urinary protein excretion was not changed. Addition of atrial natriuretic peptide to the dopamine infusion further increased urinary sodium excretion and maintained creatinine clearance at the same level. In contrast to the infusion of dopamine alone, atrial natriuretic peptide markedly increased urinary protein excretion (77 versus 229 mg min-1 m2, P less than 0.02). Furthermore, the addition of atrial natriuretic peptide elevated the urinary protein/creatinine ratio (1.55 versus 5.35, P less than 0.05), while dopamine alone did not (1.55 versus 1.45, not significant). 3. In essential hypertensive patients, dopamine and dopamine plus ANP showed renal effects similar to those of chronic glomerulonephritis; however, the urinary excretion of protein was not changed significantly. 4. These results suggest that atrial natriuretic peptide may increase urinary protein excretion mainly by increasing the permeability of the damaged glomeruli to protein rather than by simply increasing urine flow or glomerular filtration. Possible mechanisms underlying the proteinuria-increasing effects of atrial natriuretic peptide are discussed.