Renal Metabolism and Effects of the Glutamyl Derivatives of l-Dopa and 5-Hydroxytryptophan in Man

1996 ◽  
Vol 91 (2) ◽  
pp. 177-185 ◽  
Author(s):  
T. C. Li Kam Wa ◽  
S. Freestone ◽  
R. R. Samson ◽  
N. R. Johnston ◽  
M. R. Lee
Keyword(s):  
Urinary Excretion ◽  
Sodium Excretion ◽  
Competitive Inhibition ◽  
Urinary Sodium Excretion ◽  
The Other ◽  
Renal Metabolism ◽  
Dihydroxyphenylacetic Acid ◽  
Hydroxyindoleacetic Acid ◽  
Natriuretic Effect ◽  
The Given

1. Equimolar amounts of y-l-glutamyl-l-3,4-dihydroxyphenylalanine (gludopa) and γ-l-glutamyl-5-hydroxy-l-tryptophan were infused separately and together in eight healthy, salt-replete male subjects in a placebo-controlled, cross-over study to investigate whether the administration of one amine precursor affects the renal metabolism of the other and to determine whether dopamine or 5-hydroxytryptamine would be generated preferentially. The overall effect on sodium excretion was also measured when both precursors were administered simultaneously. 2. Administration of gludopa was associated with marked increases in the urinary excretion of l-dopa, dopamine and 3,4-dihydroxyphenylacetic acid, together with a rise in the urinary excretion of sodium. γ-l-Glutamyl-5-hydroxy-l-tryptophan, on the other hand, produced marked increases in the urinary excretion of 5-hydroxy-l-tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid, and this was accompanied by a slight, but non-significant, reduction in sodium excretion. About 27% of the infused dose of gludopa (on a molar basis) was recovered in the urine as dopamine whereas 15% of the given dose of γ-l-glutamyl-5-hydroxy-l-tryptophan was excreted as 5-hydroxytryptamine. 3. The urinary excretion values of l-dopa, dopamine and 3,4-dihydroxyphenylacetic acid after the simultaneous infusion of gludopa and γ-l-glutamyl-5-hydroxy-l-tryptophan were not significantly different from those observed after infusion of gludopa only. Similarly, the urinary excretion values of 5-hydroxy-l-tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid during the co-infusion were similar to those measured after administration of γ-l-glutamyl-5-hydroxy-l-tryptophan only. The net effect of the concomitant infusion of both glutamyl derivatives was an increase in urinary sodium excretion. 4. Our study in salt-replete individuals suggests that dopamine rather than 5-hydroxytryptamine was preferentially produced when equimolar amounts of their precursors were provided and that the natriuretic effect of dopamine, generated intrarenally from gludopa, was greater than the sodium retaining action of 5-hydroxytryptamine derived from γ-l-glutamyl-5-hydroxy-l-tryptophan. Comparison of the urinary metabolite data after the separate and concomitant infusion of the two glutamyl compounds provided no evidence of competitive inhibition of synthesis of either amine.

Postprandial natriuresis in humans: further evidence that urodilatin, not ANP, modulates sodium excretion

1996 ◽  
Vol 270 (2) ◽  
pp. F301-F310 ◽  
Author(s):  
C. Drummer ◽  
W. Franck ◽  
M. Heer ◽  
W. G. Forssmann ◽  
R. Gerzer ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Sodium Excretion ◽  
Salt Intake ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
High Salt ◽  
Peak Rate ◽  
High Salt Intake ◽  
Low Salt ◽  
Chloride Excretion

We examined the effects of a high-salt (100 mmol NaCl) and a low-salt (5 mmol NaCl) meal on the renal excretion of sodium and chloride in 12 healthy male upright subjects. We also measured the urinary excretion of urodilatin [ANP-(95-126)], and the plasma or serum concentrations of atrial natriuretic peptide [ANP-(99-126)], aldosterone, and renin. The high-salt meal produced a postprandial natriuresis (urinary sodium excretion from 59.0 to a peak rate of 204.6 mumol/min in 3rd h after ingestion of meal) and chloride excretion. In parallel, the urinary excretion of urodilatin increased from 35.7 to a peak rate of 105 fmol/min. The effect of high-salt intake on urinary sodium, chloride, and urodilatin excretion was significant (analysis of variance, P < 0.01), and close significant correlations were observed between urodilatin and sodium excretion (mean R = 0.702) as well as between urodilatin and chloride excretion (mean R = 0.776). In contrast, plasma ANP, which was acutely elevated 15 min after high-salt intake, was already back to low-salt values 1 h later. It did not parallel the postprandial natriuretic profile, and no positive correlation between plasma ANP and sodium excretion was observed. These results provide further evidence that urodilatin, not ANP, is the member of this peptide family primarily involved in the regulation of the excretion of sodium and chloride.

The Effect of Expanding the Blood Volume of a Dog on the Short-Circuit Current across an Isolated Frog Skin Incorporated in the Dog's Circulation

1970 ◽  
Vol 38 (6) ◽  
pp. 629-648 ◽  
Author(s):  
D. M. Nutbourne ◽  
J. D. Howse ◽  
R. W. Schrier ◽  
L. B. Talner ◽  
M. G. Ventom ◽  
...  
Keyword(s):  
Blood Volume ◽  
Sodium Excretion ◽  
Blood Circulation ◽  
Frog Skin ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
The Other ◽  
Active Sodium

1. A frog skin was incorporated into the blood circulation of a dog. Each side of the skin was supplied with blood at a constant temperature, flow and pressure. 2. In the experiments in which the blood volume of the dog was expanded with equilibrated blood, there was a fall in the short-circuit current across all eight frog skins. The fall in current began 10 min after the start of the transfusion and reached its lowest value 15–30 min after the end of the transfusion. The dog showed a simultaneous rise in urinary sodium excretion. 3. In the experiments in which the blood volume was not expanded, there was no change in the trend in the short-circuit current in five of the eight skins. There was a fall in current across the other three skins; the pattern of this fall differed from that which occurred when the blood volume was expanded. There was no rise in the rate of urinary sodium excretion in any of the dogs. 4. It is concluded that when a dog's blood volume is expanded the dog alters the concentration of some circulating substance, and that this change causes a fall in the rate of active sodium transport across the frog skin.

Excretion of endogenous digoxin-like immunoreactive factors in human urine is a function of urine flow rate.

1988 ◽  
Vol 34 (5) ◽  
pp. 960-964 ◽  
Author(s):  
B A Siegfried ◽  
R Valdes
Keyword(s):  
Urinary Excretion ◽  
Flow Rate ◽  
Human Urine ◽  
Sodium Excretion ◽  
Salt Intake ◽  
Fractional Excretion ◽  
Urinary Sodium Excretion ◽  
Urine Flow ◽  
Urine Flow Rate ◽  
Healthy Humans

Abstract We studied the effect of varying water and salt intake on the renal excretion of endogenous digoxin-like immunoreactive factors (DLIF). DLIF were measured in human urine and serum by competitive displacement of 125I-labeled digoxin from anti-digoxin antibodies. Diuresis was selectively induced in normal healthy humans by acute water ingestion, and natriuresis was preferentially induced by acute saline ingestion. We found the amount of endogenous immunoreactivity excreted in urine to be correlated with urine flow rate but not with urinary sodium excretion. Urinary excretion of DLIF, normalized to creatinine, was 3.6-fold greater at a urine flow rate of 5.5 mL/min than at 0.5 mL/min. On the other hand, saline intake increased urine flow rate 1.9-fold and increased sodium excretion threefold, but did not affect urinary excretion of DLIF. Fractional excretion of DLIF was linearly related to fractional excretion of water. This study demonstrates that normalization of DLIF values to urinary creatinine does not make DLIF excretion independent of urine flow rate and underscores the need for information on urine flow rate when DLIF measurements in urine are being interpreted.

Role of prostaglandins in the natriuresis of head-out water immersion in humans

1991 ◽  
Vol 80 (5) ◽  
pp. 481-488 ◽  
Author(s):  
Ton J. Rabelink ◽  
Hein A. Koomans ◽  
Evert J. Dorhout Mees
Keyword(s):  
Urinary Excretion ◽  
Sodium Excretion ◽  
Renal Plasma Flow ◽  
Water Immersion ◽  
Chronic Administration ◽  
Relative Increase ◽  
Similar Degree ◽  
Acute Administration ◽  
Diluting Segment ◽  
Natriuretic Effect

1. Prostaglandins may play a role in the natriuresis seen after acute circulatory challenges. To assess this role in head-out water immersion, we compared, in clearance studies, the effects of acute (24 h) and chronic (7 days) administration of indomethacin, an inhibitor of prostaglandin synthesis, on the renal response to head-out water immersion in six healthy subjects on a 200 mmol of sodium/day diet and on a 40 mmol of sodium/day diet. 2. Indomethacin caused a similar degree of sodium retention on each of these two diets. 3. During the 40 mmol of sodium/day diet, acute administration of indomethacin decreased sodium excretion before, as well as during, head-out water immersion; however, the relative increase caused by head-out water immersion was normal. After chronic administration of indomethacin, both baseline sodium excretion and the natriuresis induced by head-out water immersion were similar to those in control studies. 4. During the 200 mmol of sodium/day diet, indomethacin had no effect on baseline sodium excretion, nor on the natriuretic effect of head-out water immersion. 5. Head-out water immersion decreased tubular lithium reabsorption and increased diluting segment delivery. Despite opposite effects of indomethacin on these parameters, indomethacin did not prevent the tubular effects of head-out water immersion on either diet. However, indomethacin did prevent the marked increase in estimated renal plasma flow and the fall in filtration fraction that were observed during head-out water immersion in the absence of indomethacin (control). 6. Head-out water immersion was not associated with an increase in urinary excretion of prostaglandins. Indomethacin lowered baseline urinary excretion of prostaglandins, which did not change further during head-out water immersion. 7. We therefore conclude that renal prostaglandins are not essential for a normal natriuretic response to head-out water immersion, although they may mediate the vasodilatation induced by head-out water immersion.

Evidence in Vivo for a Circulating Natriuretic Substance in Rats after Expanding the Blood Volume

1980 ◽  
Vol 59 (6) ◽  
pp. 411-421 ◽  
Author(s):  
Catherine A. Knock ◽  
H. E. De Wardener
Keyword(s):  
Blood Transfusion ◽  
Blood Volume ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
The Other ◽  
Not Given ◽  
The Cross ◽  
The Difference

1. Five rats were volume expanded by infusing a volume of blood equivalent to one-third of the estimated blood volume. In six control experiments the same transfusion was given without expanding the blood volume, as an equal volume of blood was simultaneously removed. Sodium excretion increased significantly more after the blood volume was expanded than in the control experiments. 2. Pairs of rats placed on opposite scale pans of a trip balance were cross-circulated by means of arteriovenous bypasses. The blood volume of the rats could be kept constant by keeping the balance in equilibrium. 3. One of each pair of rats received a blood transfusion which either did or did not expand its blood volume. Sodium excretion was measured in the transfused rat and in the recipient rat, the blood volume of which was kept constant. 4. Sodium excretion in the six recipient rats cross-circulated with rats with an expanded blood volume was not significantly different from that in six recipient rats, cross-circulated with rats given a transfusion which did not expand the blood volume. 5. The cross-circulation experiments were repeated, with the difference that the urine of the transfused rat was reinfused. Under these conditions, sodium excretion in 11 recipient rats cross-circulated with blood volume expanded rats was significantly greater than in eight recipient rats cross-circulated with rats given a transfusion which did not expand the blood volume. 6. In cross-circulation experiments in which a blood transfusion was not given urine reinfusion of one rat did not affect sodium excretion of the other rat. 7. It is concluded that the rise in urinary sodium excretion which occurs in an isovolaemic recipient rat cross-circulated with a urine reinfused rat with an expanded blood volume is due to a change in the concentration of a circulating substance.

Vascular sensitivity to prostaglandin I2 and urinary excretion of 6-keto-prostaglandin F1α in conscious dogs

1986 ◽  
Vol 71 (5) ◽  
pp. 527-532 ◽  
Author(s):  
Robert L. Jones ◽  
Michael L. Watson
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Sodium Excretion ◽  
Hydrolysis Product ◽  
Urinary Sodium Excretion ◽  
Renal Haemodynamics ◽  
Conscious Dogs ◽  
Gas Chromatography Mass Spectrometry ◽  
Prostaglandin I2 ◽  
Stable Isotope Dilution

1. A method is described for measuring the urinary excretion of 6-keto-prostaglandin F1α, the stable hydrolysis product of prostaglandin I2, by stable isotope dilution gas chromatography–mass spectrometry. 2. Three different doses of prostaglandin I2 were infused intravenously into conscious dogs and the effects on systemic and renal haemodynamics and urinary sodium excretion were observed. 3. The two highest infusion rates of prostaglandin I2 (15 and 30 ng min−1 kg−1 body weight) induced significant decreases in systematic blood pressure and dose-related increases in sodium excretion, but no change in renal haemodynamics. 4. There was a linear relationship between urinary excretion of 6-keto-prostaglandin F1α and the rate of infusion of prostaglandin I2. 5. The calculated basal rate of entry of prostaglandin I2 into the systematic circulation in conscious dogs is 4 ng min−1 kg−1 body weight, which is substantially higher than that previously reported in man.

Interaction between neural and nonneural mechanisms controlling renin secretion rate

1984 ◽  
Vol 246 (5) ◽  
pp. F620-F626 ◽  
Author(s):  
U. C. Kopp ◽  
G. F. DiBona
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Neural Mechanisms ◽  
Secretion Rate ◽  
The Other ◽  
Renin Secretion ◽  
Renal Nerves ◽  
The Right

The interaction between the neural and nonneural mechanisms in the control of renin secretion rate was studied in anesthetized vagotomized dogs at renal arterial pressures of 170, 130, 90, and 50 mmHg. Left renal nerves were stimulated (RNS) at either 0.075, 0.3, or 0.7 Hz and the right kidney was denervated. At spontaneous renal arterial pressure RNS at 0.075, 0.3, and 0.7 Hz decreased renal blood flow 0, 1 +/- 0, and 2 +/- 1%, respectively, and urinary sodium excretion 0, 2 +/- 1, and 22 +/- 3%, respectively. RNS at 0.075 Hz augmented renin secretion rate at 50 mmHg by 1,806 +/- 505 ng/min; there was no augmentation at 90, 130, and 170 mmHg. RNS at 0.3 Hz augmented renin secretion rate at 50 and 90 mmHg by 2,635 +/- 824 and 1,197 +/- 289 ng/min, respectively; there was no augmentation at 130 and 170 mmHg. RNS at 0.7 Hz augmented renin secretion rate at 50, 90, and 130 mmHg by 1,421 +/- 287, 747 +/- 172, and 273 +/- 163 ng/min, respectively; there was no augmentation at 170 mmHg. RNS at 0.075 Hz to one kidney and 0.7 Hz to the other kidney in the same dog demonstrated that the renin secretion rate was greater with RNS at 0.7 Hz than with 0.075 Hz at 50 and 90 mmHg but not at 130 and 170 mmHg. We conclude that the nonneural and neural mechanisms interact in the control of renin secretion rate. The degree of interaction depends on the level of renal arterial pressure and the intensity of RNS.

Plasma Renin, Urinary Sodium Excretion and Vascular Disease

1974 ◽  
Vol 48 (s2) ◽  
pp. 127s-129s
Author(s):  
A. E. Doyle ◽  
K. G. Chua ◽  
S. Duffy ◽  
W. J. Louis
Keyword(s):  
Plasma Renin Activity ◽  
Urinary Excretion ◽  
Vascular Disease ◽  
Sodium Excretion ◽  
Mild Hypertension ◽  
Sodium Intake ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Renin Activity

1. Urinary sodium excretion and plasma renin activity have been measured in a group of persons with untreated mild hypertension and in a control normotensive group. 2. Preliminary analyses of the data indicate that the daily sodium excretion was significantly higher in the hypertensive group but the plasma renin activity did not correlate significantly with the urinary excretion of sodium. 3. These findings suggest that sodium intake was significantly greater in a population with mild hypertension than in a comparable normotensive group.

Interference with Measurement of 3-Methoxy-4-hydroxymandelic Acid and 5-Hydroxyindoleacetic Acid by Reducing Metabolites

1974 ◽  
Vol 20 (5) ◽  
pp. 607-610 ◽  
Author(s):  
Jerome M Feldman ◽  
Susan S Butler ◽  
Barbara A Chapman
Keyword(s):  
Urinary Excretion ◽  
Homovanillic Acid ◽  
Analytical Techniques ◽  
Homogentisic Acid ◽  
Gentisic Acid ◽  
Dihydroxyphenylacetic Acid ◽  
Apparent Decrease ◽  
Hydroxyindoleacetic Acid

Abstract Using standard analytical techniques, we noted a decrease in the urinary excretion of 3-methoxy-4-hydroxymandelic acid and 5-hydroxyindoleacetic acid in a patient with alcaptonuria, and in subjects receiving aspirin or L-dopa [3-( 3,4-dihydroxyphenyl)-L-alanine]. This apparent decrease in excretion of the two compounds is an artifact produced by metabolites in urine, such as homogentisic acid, gentisic acid, 3,4-dihydroxyphenylacetic acid, or homovanillic acid.

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