A natriuretic principle derived from kidney tissue of volume-expanded rats

Gonick, Harvey C.; Saldanha, Leopoldo F.

doi:10.1172/jci108087

Cited by 45 publications

(18 citation statements)

References 27 publications

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“…After the elution of the salt peak (5), the osmolality dropped to Ͻ100 mOsm/kg. Following this step, ten 10-ml fractions were collected, lyophilized, resuspended (in 1.0 ml of water), and assayed for inhibition of SCC in the frog skin (10). Active fractions, as already defined, from the Sephadex column were then injected into a semiprep C18 column (Synergi 4u Hydro-RP 80A 250 ϫ 10 mm, 4 m; Phenomenex, Torrance, CA).…”

Section: Methodsmentioning

confidence: 99%

“…In numerous experimental models, several groups had consistently observed natriuretic activity from a small molecule (Ͻ1,000 Da) contained in mammalian urine that eluted as a postsalt peak in Sephadex G-25 gel chromatography. A natriuretic substance was shown to be present in urine and/or serum extracts of patients with chronic renal disease (CRD) (4,5), normal man (6), salt-loaded man (7,8), volume-loaded man (9), and volume-loaded rat (10). Although inferred in the experiments mentioned earlier, no molecule was ever isolated or identified.…”

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confidence: 97%

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Identification of xanthurenic acid 8- O -β- d -glucoside and xanthurenic acid 8- O -sulfate as human natriuretic hormones

Cain¹,

Schroeder

Shankel³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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showed that when these two variables were controlled, the kidney was still able to increase sodium excretion in response to a salt load. Several lines of evidence argued for a small-molecule signal as a definitive modulator of sodium excretion by the kidney. However, the chemical nature of the suspected natriuretic agent remained unknown. Here we report the identification and natriuretic activity of two closely related small molecules isolated from human urine, xanthurenic acid 8-O-␤-D-glucoside and xanthurenic acid 8-O-sulfate. The two compounds were partially purified by activity-guided fractionation and subsequently identified by using NMR spectroscopic analyses of enriched active fractions. Both compounds caused substantial and sustained (1-to 2-h) natriuresis in rats and no or minimal concomitant potassium excretion. We believe these compounds constitute a class of kidney hormones that also could influence sodium transport in nonkidney tissues given that these tryptophan metabolites presumably represent evolutionarily old structures.diuresis ͉ kidney ͉ nonpeptidic ͉ sodium homeostasis ͉ NMR spectroscopy

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 97%

Identification of xanthurenic acid 8- O -β- d -glucoside and xanthurenic acid 8- O -sulfate as human natriuretic hormones

Cain¹,

Schroeder

Shankel³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Previous work from this laboratory 14 has demonstrated that a natriuretic factor also can be isolated from kidneys of volume-expanded rats but is not found in kidneys of hydropenic rats. In the present study we have shown in addition that this factor inhibits transepithelial sodium transport by isolated frog skin in a dose-dependent manner.…”

mentioning

confidence: 88%

“…Fraction III from hydropenic rats was not tested because our earlier experiments had demonstrated clearly that the fraction from expanded, but not from hydropenic, rat kidneys contained natriuretic activity. 14 …”

Section: Rat Assay In Vivomentioning

confidence: 99%

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Further characterization of the natriuretic factor derived from kidney tissue of volume-expanded rats. Effects on short-circuit current and sodium-potassium-adenosine triphosphatase activity.

Hillyard¹,

Lu²,

Gonick³

1976

Circulation Research

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SUMMARY Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected Co column chroniatography. The fraction eluting within the range of partition coefficients (K av ) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 ftg/ml, fraction III from expanded rat kidney inhibited SCC by 21 ± 5% (P < 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 ± 8%. In a dose-response study, 50, 150, 500, and 1,500 pg/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, i.OOOVand 1,500 M g/ml inhibited Na-K-ATPase activity by 11, 22, arid 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction HI also produced significant natriuresis in vivo at a dose of 500 ^g/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volumeexpanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.SEVERAL STUDIES now have shown that natriuretic factors can be found in both the serum and the urine of volume-expanded or uremic animals and humans.1 " 9 These factors not only produce a natriuresis when injected into test animals but also inhibit transepithelial sodium transport in anuran membrane preparations such as the isolated frog skin or toad bladder.1 ' 10 ' 13 The term "antinatriferic" has been used to describe this latter effect.11 In a recent study, kaplan et a!.13 have shown that the natriuretic factor obtained from uremic urine increases intracellular sodium content of and decreases pyruvate oxidation by isolated toad bladder cells. These findings suggest that this natriuretic factor inhibits active sodium transport either through interference with ATP generation via the tricarboxylic acid cycle or with some step in the active transport sequence, possibly the transport enzyme, Na-K-ATPase.Previous work from this laboratory 14 has demonstrated that a natriuretic factor also can be isolated from kidneys of volume-expanded rats but is not found in kidneys of hydropenic rats. In the present study we have shown in addition that this factor inhibits transepithelial sodium transport by isolated frog skin in a dose-dependent manner. Furthermore, the factor inhibits Na-K-ATPase activity of Received November 21, 1974; accepted for publication December 22, 1975. pooled rat kidney cortex homogenates with a similar dose-response relationship. Methods PREPARATION OF MATERIALFemale Sprague-Dawley rats (250-300 g) were infused with 0.9% saline through a jugular venous cannula. An amoun...

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The pathology of marginal renal function

Favre

Bricker

1981

Reviews of Physiology, Biochemistry and Pharmacology

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A natriuretic principle derived from kidney tissue of volume-expanded rats

Cited by 45 publications

References 27 publications

Identification of xanthurenic acid 8- O -β- d -glucoside and xanthurenic acid 8- O -sulfate as human natriuretic hormones

Identification of xanthurenic acid 8- O -β- d -glucoside and xanthurenic acid 8- O -sulfate as human natriuretic hormones

Further characterization of the natriuretic factor derived from kidney tissue of volume-expanded rats. Effects on short-circuit current and sodium-potassium-adenosine triphosphatase activity.

The pathology of marginal renal function

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