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J F Cloix

Publications and source records attributed to J F Cloix.

At least 37 records · Page 2Linked to original sources
PubMed1986

Recent progress on an endogenous digitalislike factor in hypertension.

Evidence exists that demonstrates the relationship between a natriuretic factor, or Na+, K+-ATPase inhibitor, and volume expansion in man. Patients having extracellular volume expansion have been studied for the effect of their plasma on erythrocyte [3H]ouabain binding. High levels of ouabainlike activity were found in plasma from acromegalic patients and patients with chronic renal failure. High levels were also observed in some hypertensive patients. A partial purification of such a compound was performed from the urine of hypertensive patients. The various steps of purification achieved a 400,000-fold purified compound of apparent homogeneity. The inhibitor was extracted from 140 liters of urine of 21 donors (hypertensive patients and normotensive offspring of hypertensive patients). The purification steps included flash chromatography, anionic exchange, and reversed-phase HPLC on RP 18, diphenyl and phenyl packings. Nuclear magnetic resonance and mass spectrometry indicated a nonpeptidic compound, which was possibly a steroid with a low molecular mass (less than 500 daltons).

Adult↗
PubMed1985

High yield-purification of a urinary Na+-pump inhibitor.

A Na+-pump inhibitor was purified from 140 liters of human urine to an apparent homogeneity. Tracing of the inhibitor during the different steps of purification was achieved by simultaneous determination of its capacity to inhibit the activity of Na+,K+-ATPase and ouabain binding, and to cross-react with antidigoxin antibodies. The final purification achieved a 400,000 fold. The purification steps included flash chromatography, anionic exchange chromatography, and reversed-phase HPLC on RP18, diphenyl and phenyl packings. NMR studies indicated that the final product was a non-peptidic, possibly steroidal compound. Its molecular weight as determined by mass spectrometry was 431.

Animals↗
PubMed1985

Affinity chromatography for human Na+, K+-ATPase inhibitors in plasma and urine.

Semi-purified dog kidney Na+,K+-ATPase cross-linked with ovalbumin was used in batch-wise affinity chromatography for the detection of endogenous Na+,K+-ATPase inhibitor in human plasma and urine. Ammonium acetate 1 M washed off the endogenous inhibitor from the immobilized enzyme. The inhibitory activity of the eluate from hypertensive plasma and urine was significantly higher (p less than 0.0025, n = 5 and p less than 0.005, n = 6 respectively) than that of normotensive. This latter was correlated with the ability of plasma from the same subjects to compete with ouabain binding to erythrocytes. Plasma and urine extracts inhibited the activity of Na+, K+-ATPase in a dose-dependent manner as ouabain does and were shown to contain 3 or 4 active compounds by high pressure liquid chromatography. The activity of some of these compounds was lost after peptidase treatment. These data support the heterogeneity of endogenous inhibitors of Na+,K+-ATPase activity in plasma and urine.

Animals↗
PubMed1985

Recent advances on endogenous Na+,K+-ATPase inhibitors: clinical investigation and purification.

Evidence exists which demonstrates the relationship between a Natriuretic Factor or Na+,K+-ATPase inhibitor and volemic expansion, both in man and animal. Patients having extracellular volume expansion have been studied for the effect of their plasma on erythrocytes 3H-ouabain binding. High levels of ouabain-like activity was found in plasma from acromegalic patients and patients with chronic renal failure. High levels were also observed in some hypertensive patients. A partial purification of such a compound was performed from urine of hypertensives. The partially purified compound inhibited to a greater extent the Na+,K+-ATPase semi-purified from dog kidney than that from sheep brain. The present data are consistent with the possible regulation of the activity or the secretion of plasma ouabain-like activity by extracellular volume.

Acromegaly↗
PubMed1985

Chemical, experimental, and clinical studies on endogenous ouabain-like substance in hypertension.

A heat-stable, low molecular weight, anionic substance(s) capable of inhibiting 3H-ouabain binding and Na+-K+-ATPase activity could be extracted from human urine and plasma. The level of the inhibitor was elevated in 40%-50% of essential hypertensives, compared to controls, and also in some of the offspring of hypertensive parents. Higher levels of the inhibitor were measured in patients treated with beta-blocking agents than in those treated with diuretics. The inhibitor extracted from plasma also appeared capable of (1) inhibiting the uptake of serotonin in human platelets, an Na+-dependent mechanism, and (2) inducing an increase in blood pressure when injected intracerebroventricularly. From these various data, we propose that the increase in the endogenous inhibitor may play a role in essential hypertension and may modulate, at least partially, some of the various cell functions that depend on a transmembrane Na+ gradient, including cellular excitability.

Adult↗
PubMed1984

Purification from human plasma of endogenous sodium transport inhibitor(s).

Na+,K+-ATPase inhibitors extracted from plasma of healthy human subjects displaced 3H-ouabain binding to human erythrocytes and inhibited the Na+ efflux catalyzed by the Na+,K+-pump and unexpectedly the Na+,K+-cotransport system without alteration of the Na+,Na+-exchange or the Na+ passive permeability. This suggests the presence in healthy human plasma of endogenous factors with ouabain-like and furosemide-like activities.

Biological Transport↗
PubMed1984

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

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 acetonitrile 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 (1P, 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 (1U and 2U). Peak 2U cross-reacted with anti-digoxin 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.

Antibodies↗
PubMed1984

Circulating digitalis-like compounds in essential hypertension.

Inhibitors of the Na+ pump have been proposed as participating in sodium excretion, extracellular fluid regulation, and in the rise of blood pressure. The presence of digitalis-like compounds in human plasma has been investigated by comparing the effects of plasma extracts to those of ouabain in 4 tests. - competition with ouabain for binding to the Na+ pump, - inhibition of Na+ and K+ dependent hydrolysis - inhibition of serotonin uptake by human platelets - central hypertensive effect Plasma fractions exhibited digitalis-like properties in the 4 tests. The effects of plasma extracts of 42 normotensive subjects (21 with family history of hypertension) and 38 patients with essential hypertension (15 with antihypertensive treatment) and 9 patients with chronic renal failure were compared. Plasma from Forty per cent of untreated hypertensive patients and normotensives with hypertensive heredity had a high inhibition level. Inhibition was enhanced in beta-blocker treated patients and decreased in those on diuretics. No digitalis-like activity was observed in uremic plasma. These observations strongly suggest the presence of digitalis-like compound(s) in human plasma and point to its possible association with hypertension.

Adult↗
PubMed1984

[Affinity chromatographic study of the changes in the endogenous Na+-K+-ATPase inhibitor during sodium loading in man].

Semi-purified dog kidney Na+-K+-ATPase was cross-linked with ovalbumin. This immobilized enzyme was able to hydrolyse ATP and this hydrolysis was ouabain-sensitive. It was then used in batch wise affinity chromatography for the detection of endogenous Na+-K+-ATPase inhibitor in human plasma and urine. Ammonium acetate 1 mM washed off the endogenous Na+-K+-ATPase inhibitor from the immobilized enzyme. The inhibitory activity of the eluate from hypertensive plasma was significantly higher (p less than 0.0025, n = 6) than that of normotensive plasma. Similar results were obtained (n = 3) from human urine eluates during salt loading as compared to control urine.

Animals↗
PubMed1984

Investigation of the endogenous Na+-pump inhibitor in essential hypertension and blood volume expansion.

The digitalis-like activities of plasma extracts from 108 patients and normal subjects were measured by their ability to compete with ouabain for binding to the digitalis sites of the Na+-pump. High levels were found in 18 of 54 untreated patients with moderate hypertension, 10 of 14 patients with end-stage renal failure and six patients with active acromegaly. These levels returned to control values after dialysis in the patients with renal insufficiency and high levels of the inhibitor, and after successful surgery and cobalt therapy in seven acromegalic patients. An increase in circulating Na+, K+-ATPase inhibitor was also found in rats after chronic sodium loading. These results indicate that levels of the circulating compound with digitalis-like properties do not result from high blood pressure but, rather, are related to blood volume and Na+ balance.

Acromegaly↗
PubMed1984

Clinical and biochemical approach of a circulating Na+-pump inhibitor.

Inhibition of the activity of semipurified renal Na+, K+-ATPase and of 3H-Ouabain binding to erythrocytes was used to titrate the level of a plasmatic endogenous inhibitor of the Na+, K+-pump. The inhibition effect of plasma extracts was specific and unrelated to vanadate, calcium and products of proteolysis. Similar results were obtained with the two procedures. An endogenous pump inhibitor could be detected in 28 plasmas of the 42 normotensives investigated so far. In 18 out of 21 normotensives born of hypertensive parent(s) the level was found to be higher than that observed in normotensive controls devoid of hypertensive heredity. 13 untreated essential hypertensives out of 21 also exhibited higher levels of the sodium-potassium pump inhibitor. Plasma levels of the inhibitor appear stable during several months in male subjects. No clear relationship could be established either in normotensives or hypertensives between the pump inhibitor level, the urinary output of Na+, and blood pressure. Neither could any relationship be established between the inhibitor and the intraerythrocytic Na+ concentration. The accuracy of the methodology allows a large scale clinical investigation. It can also be used in the purification of the substance, and preliminary results precised that its molecular weight was inferior to 1 000 daltons and that it was anionic. Purified fractions were obtained after gel filtration, ion exchange chromatography, and high pressure liquid chromatography. Preliminary results suggest that the purified fraction may interfere with the mechanisms of hypertension. They inhibited the Na+-dependent serotonin uptake by human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1984

[Essential arterial hypertension, cellular intolerance to sodium].

Much experimental and clinical evidence points to the fact that increased intracellular Na+ concentration could play an important pathogenic role in hypertension, especially where cells of excitable tissues are concerned. Active extrusion of Na+ (from the cells to the extracellular space) depends mainly on the activity of the system of membrane transport known as the Na+ pump. The extrusion of Na+ occurs in exchange for K+ and the activity of the pump depends on the enzyme Na+-K+-ATPase. The Na+ pump is inhibited by cardiotonic glycosides such as digitalis and ouabain . The results obtained in our laboratory suggest that the activity of the Na+ pump is controlled by an endogenic system acting in a similar manner to ouabain and digitalis. Experimental and clinical studies show: -- that the administration of Na+ increases the inhibitor effect both in urine and plasma; -- that the inhibitor is increased in about 50 p. 100 of patients with essential hypertension; -- that this increase seems to depend on familial or genetic factors. The biochemical identification of this endogenic inhibitor is now under way; it has a small molecular weight (less than 3000), is thermostable and anionic. This factor could have both a regulating role on Na+ turnover and a pathological role in hypertension. Its activity comes into competition cations also capable of inhibiting the Na+ pump, including K+.

Animals↗
PubMed1983

[Purification of an endogenous inhibitor of sodium-potassium-ATPase].

From human plasma of healthy subject, an inhibitor of Na+, K+-ATPase was prepared, using a gel filtration followed by anion exchange chromatography and by HPLC on reverse phase. This low molecular weight (less than 1,500 dalton) inhibitor is a substance which possesses anionic charges, and is absorbed on reverse phase. It inhibits Na+, K+-ATPase activity and the 3H-ouabain binding on human red blood cells.

Animals↗
PubMed1983

Characterization and partial purification of 'renocortins': two polypeptides formed in renal cells causing the anti-phospholipase-like action of glucocorticoids.

1 Anti-inflammatory steroids reduce prostaglandin E2 (PGE2) synthesis in rat renomedullary interstitial cells in culture by inhibiting the release of arachidonic acid from membranous phospholipid stores, exhibiting antiphospholipase-like properties. 2 After treatment of the cells with dexamethasone 10(-6)M, these cells release a protein in the supernatant. 3 This supernatant is able to inhibit PGE2 secretion in untreated cells and to inhibit phospholipase A2 activity in an in vitro system. 4 Using chromatofocusing separation, we showed that two distinct proteins exist with isoelectric points of 5.8 and 8.3. 5 Using gel permeation separation, we showed that two proteins exist with apparent molecular weights of 15,000 and 30,000 daltons. 6 We conclude that, in renal cells in culture, anti-inflammatory steroids induce the synthesis and the release of two polypeptides which we have named 'Renocortins' (induced by corticoids in renal cells) causing the antiphospholipase-like action of glucocorticoids. 7 Our results are in good agreement with others, but as renal cells are not directly involved in the inflammatory process, we suggest that this steroid-induced phenomenon is not solely involved in the inflammatory reaction but is of more general physiological relevance.

Animals↗