Further Characterization and Evidence for a Precursor in the Formation of Plasma Antinatriferic Factor

Gruber, Kenneth A.; Buckalew, Vardaman M.

doi:10.3181/00379727-159-40371

Cited by 41 publications

(23 citation statements)

References 7 publications

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“…The high molecular substance that we obtained from the atrial extracts had an immediate onset and transient duration (<30 min) of action and, therefore, would appear to differ from the previously reported materials. Furthermore, the low molecular weight peptide fraction that we have resolved is much larger than the previously reported low molecular weight (-500) peptide (11).…”

Section: Discussionmentioning

confidence: 74%

“…A number of investigators have reported the existence of two different natriuretic factors in plasma or urine. The high molecular weight peptide (variously reported to be >1,500-10,000 and <50,000) was suggested to be a precursor of the lower molecular weight substance as an explanation of the delayed onset (10-20 min) and long-lasting (2-3 hr) natriuresis observed in assay rats (8)(9)(10)(11). The high molecular substance that we obtained from the atrial extracts had an immediate onset and transient duration (<30 min) of action and, therefore, would appear to differ from the previously reported materials.…”

Section: Discussionmentioning

confidence: 99%

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Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Currie¹,

Geller²,

Cole³

et al. 1984

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

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Mammalian cardiac atria possess several unidentified biologically active peptides. Fractionation of rat atrial extracts by gel filtration chromatography revealed two major fractions [apparent molecular weights of 20,000-30,000(peak I) and <10,000 (peak II)], both of which were potent natriuretic agents (eliciting a 25-fold increase in sodium excretion) and smooth muscle relaxants. Vigorous treatment with trypsin (100 units/ml at 370C for 15 min) of both fractions abolished all biological activity. Further purification of the lower molecular weight fraction (peak II) by ion-exchange chromatography indicated two subfractions that possessed potent natriuretic activity and that preferentially relaxed either intestinal (designated peak IIA) or vascular (peak IIB) smooth muscle assay tissues. The similarity of the biological effect of the high (peak I) and low (peak II) molecular weight peptides led us to test the possibility of precursor-product relationship.Mild proteolytic treatment of the high molecular weight peptide with trypsin (1 unit/ml at room temperature) markedly enhanced the smooth muscle relaxant activity. Subsequent analysis of the trypsin (1 unit/ml)-treated high molecular weight peptide (peak I) by gel filtration and ion-exchange chromatography revealed that the peptide now resembled the low molecular weight peptides (peaks IIA and IIB) present in the original atrial extract. These data suggest that the cardiac atria contain a relatively inactive (smooth muscle relaxant) high molecular weight peptide and suggest that biologically active low molecular weight peptides can subsequently be generated by proteolytic cleavage.Recent evidence indicates that granules typical of protein secretory cells are localized in mammalian atria. The granules may be the source of an endocrine substance(s) that possibly regulates fluid balance (1, 2). The contents and function of granules located in mammalian cardiac atria remain to be established. A possible homeostatic function is implied by the demonstration that atrial stretch or myocardial volume overload cause a natriuresis and diuresis (3) and that atrial (but not ventricular) extracts possess natriuretic and diuretic activity when administered to rats (4-6). Partial purification of the atrial extract indicates the presence of several fractions with natriuretic activity (5, 6). We discovered that the crude rat atrial, but not the ventricular, extract possesses potent smooth muscle relaxant activity on isolated vascular and intestinal muscle strips (7). Because the atria are the site of fluid volume receptors, they would appear to be the ideal site for the storage and release of bioactive peptides that could participate in the fluid balance by influencing vascular tone and renal function. We separated rat atrial extracts by gel filtration into low molecular weight (<10,000) and high molecular weight (20,000-30,000) fractions, both of which were potent natriuretics when administered intravenously to rats and both of which were spasmolytic on isolated smooth mu...

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Currie¹,

Geller²,

Cole³

et al. 1984

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

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“…While the existence of this endogenous factor(s) is generally accepted, the number and structure of the inhibitor(s) is yet to be determined. For example, two inhibitors were found in the plasma of salt-loaded dogs [5,6], 3 in the plasma of healthy humans [7], 4 in the plasma of patients with fulminant hepatic failure [8] and only 1 in the plasma of uremic patients [9]. In contrast, only a single active substance has been identified in the urine of salt-loaded humans [lO-141 or salt-loaded dogs [ 151.…”

Section: Introductionmentioning

confidence: 99%

“…and determination of the Na+,K+-ATPase inhibiting substances have also varied. The reported methods include chromatography on Sephadex G-25 [f&9,13], ion-exchange chromatography [7], and combinations of ion-exchange and reversephase chromatography [5,6,15]. The same method has not been applied to both plasma and urine.…”

Section: Introductionmentioning

confidence: 99%

Measurement of endogenous Na⁺,K⁺‐ATPase inhibitors in human plasma and urine using high‐performance liquid chromatography

Crabos¹,

Wainer²,

Cloix³

1984

FEBS Letters

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This study was undertaken to assess endogenous Na+,K+-ATPase inhibitors in both plasma and urine in the same subjects. Samples were chromatographed on reverse-phase HPLC using an a&on&rile gradient and the eluent screened using Na+,K+-ATPase inhibition and cross-reaction with anti-digoxin antibodies.The donors were divided into inhibiting and non-inhibiting subjects using a previously described method, plasma action on ouabain binding and on Na+,K+-ATPase activity. Three Na+,K+-ATPase inhibitors (lP, 2P and 3P) were detectable in plasma; the antibodies cross-reaction of the peaks 2P and 3P were larger than that of peak 1P. The peaks 2P and 3P were significantly higher in inhibiting subjects as compared to non-inhibiting subjects. The 24-h urine is resolved into two peaks inhibiting Na+,K+-ATPase activity (IU and 2U). Peak 2U cross-reacted with antidigoxin antibodies to a greater extent than peak 1U and is significantly larger in inhibiting subjects in terms of Na+,K+-ATPase inhibition. These data support the heterogeneity of human Na+,K+-ATPase inhibitor in both plasma and urine.

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“…The plasma was separated and allowed to sit at room temperature for 30 minutes to enhance HPIF activity, if any. 16 The plasma was then boiled for 5 minutes at 100°C to precipitate serum proteins and to inactivate known vasoactive hormones. The boiled plasma was then centrifuged at 36,000 g for 90 minutes.…”

Section: Preparation Of Boiled Plasma Supernates For Assay Of Hpifmentioning

confidence: 99%

Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension.

1987

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SUMMARY This review summarizes our bioassay methods for determining the level of humoral sodium pump inhibiting factor after acute volume expansion in experimental animals and humans, and in low renin experimental and human essential hypertension. In brief, ouabain-sensitive **Rb uptake and membrane potential in blood vessels from normal animals are measured after incubation in plasma supernate from experimental subjects and animals and their respective controls. The data show that humoral sodium pump inhibitor is elevated after acute volume expansion in normal animals (dogs and rats) and in normal humans. The level of inhibitor is also elevated in patients with low renin essential hypertension and in experimental animals with low renin, volume-dependent types of hypertension, namely, one-kidney, one wrapped hypertension in dogs, and one-kidney, one clip and reduced renal mass-saline hypertension in rats. Humoral sodium pump inhibiting factor inhibits the Na + -K + pump in the cardiovascular system. Such inhibition by other means (hypokalemia, cardiac glycosides) activates the system. Therefore, we also discuss the possible role of humoral sodium pump inhibitor in low renin volume-dependent hypertension. Increased salt intake or decreased salt excretion leads to elevated blood pressure. The pressure rises slowly, suggesting that the increase cannot be explained by volume expansion per se. In these types of hypertension, plasma renin activity is decreased, and converting enzyme inhibitors and angiotensin antagonists have minimal effects on blood pressure. Catecholamine blood levels are decreased after increased salt ingestion or decreased salt excretion and therefore cannot explain the elevated blood pressure.Recent studies in our laboratory suggest that Na + ,K + -adenosine triphosphatase (ATPase) and

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Further Characterization and Evidence for a Precursor in the Formation of Plasma Antinatriferic Factor

Cited by 41 publications

References 7 publications

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Measurement of endogenous Na⁺,K⁺‐ATPase inhibitors in human plasma and urine using high‐performance liquid chromatography

Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension.

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Further Characterization and Evidence for a Precursor in the Formation of Plasma Antinatriferic Factor

Cited by 41 publications

References 7 publications

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Proteolytic activation of a bioactive cardiac peptide by in vitro trypsin cleavage.

Measurement of endogenous Na+,K+‐ATPase inhibitors in human plasma and urine using high‐performance liquid chromatography

Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension.

Contact Info

Product

Resources

About

Measurement of endogenous Na⁺,K⁺‐ATPase inhibitors in human plasma and urine using high‐performance liquid chromatography