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Biomedical subjects

M A Devynck

Publications and source records attributed to M A Devynck.

At least 145 records · Page 8Linked to original sources

[Chronic sodium loading and circulating inhibitor of Na+,K+-ATPase in rats].

The effects of chronic sodium load on the activity of a circulating inhibitor of the Na+, K+-pump were measured in male Wistar rats. The inhibition by deproteinized plasma of renal Na+, K+-ATPase was higher in rats with high Na+ intake than in control animals (53.4 +/- 2.0 mumoles Pi.h-1 X mg-1 vs 66.6 +/- 2.6 mumoles Pi.h-1 X mg-1, p less than 0.01). The simultaneous rise in systolic blood pressure and the decrease in the hematocrit suggest that blood pressure, volemic expansion and the activity of this inhibitor may be somehow linked.

Animals↗

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↗

Altered active sodium and calcium transport by heart sarcolemmal membranes from young spontaneously hypertensive rats: modulation by calmodulin.

Active transport of Na+,K+ and Ca2+ was compared in heart plasma membranes from 3-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). ATP-dependent Ca2+ accumulation, which reflects Ca2+, Mg2+-ATPase activity, was higher in SHR than in WKY membranes. At a free calcium concentration of 4 X 10(-7)M, the addition of 2 X 10(-7)M calmodulin enhanced the active Ca2+-transport more in WKY than in SHR vesicles. Na+- and K+-dependent ATPase activity was two fold higher in SHR than in WKY. From ouabain binding studies this seemed to be due to an increased density of enzyme units. Physiological concentrations of calmodulin and calcium ions reduced Na+,K+-ATPase activity in the two strains but more in SHR than in WKY. This study demonstrates that active Na+ and Ca2+ transport is enhanced in young SHR; the Ca2+-calmodulin complex may regulate Na+,K+-ATPase activity and sensitivity of Na+,K+-ATPase and Ca2+,Mg2+-ATPase activities to Ca2+-calmodulin differs between SHR and WKY.

Aging↗

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↗

Central hypertensive effect of ouabain in rats.

Ouabain was infused into the third cerebral ventricle of fully conscious, pentobarbital-anaesthetized or urethane-anaesthetized rats. Convulsive seizures occurred in the freely moving rats. The blood pressure of the pentobarbital-anaesthetized rats rose inconsistently. However, in those animals, anaesthetized with urethane, a consistent cardiovascular response was observed with an initial bradycardia, followed by a progressive increase in both the blood pressure and the heart rate. The hypertension was associated with a rise in the CSF potassium level. Tachyphylaxis to these responses was observed.

Anesthesia↗

[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↗

Measurement of digitalis-like compound in plasma: application in studies of essential hypertension.

A digitalis-like compound was detected in human plasma by tritiated ouabain competition binding to the sodium pump. The study comprised analyses of plasma extracts from 17 normal controls, 17 normotensive subjects with one or both parents hypertensive, and 16 patients with untreated essential hypertension. In two thirds of the untreated hypertensive and several of the normotensive subjects with a family history of hypertension the potency of the digitalis-like compound, as measured by its interference with ouabain binding, was significantly greater than in the controls. In the untreated hypertensive patients the potency of the compound was significantly correlated with the urinary sodium output. Measurement of this salt-related, digitalis-like compound may be useful in clinical studies of hypertension.

Adolescent↗

Nomifensine antagonizes the ouabain-induced increase in dopamine metabolites in cerebrospinal fluid of the rat.

The effect of the Na+, K+-ATPase inhibitor, ouabain, on cerebrospinal fluid dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) levels was studied in pentobarbitone-anesthetized rats. An intracerebroventricular injection of ouabain (100 nmol) dramatically increased DOPAC and HVA levels. A dopamine uptake inhibitor, nomifensine (10 mg/kg i.p.) injected prior to ouabain, completely abolished the effect of ouabain on dopamine metabolites. These results are in agreement with the ouabain-induced increase in dopamine efflux described in vitro and favour the role of a carrier-mediated cytosolic release of dopamine.

3,4-Dihydroxyphenylacetic Acid↗

[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↗

Plasma endogenous sodium pump inhibitor in essential hypertension.

The presence of circulating Na+ pump inhibitors was investigated in hypertensive subjects using inhibition of ouabain binding to the pump and of Na+, K+-ATPase activity as tests. Plasma extracts from nearly half the normotensive subjects who were offspring of hypertensive parents as well as the essential hypertensive subjects were potent inhibitors. Three fractions, extracted from plasma, exhibited ouabain-like properties concerning competition for binding, inhibition of the Na+, K+-ATPase and of Na+-dependent serotonin uptake by platelets. When injected intracerebroventricularly, one of these fractions also induces a rise in blood pressure, as does ouabain. These results demonstrate the presence in some plasma of digitalis-like substances.

Animals↗

[Reduction of platelet serotonin in major depression (endogenous depression)].

Serum serotonin (5-HT) levels were measured in several patients with psychiatric disorders using high pressure liquid chromatography with electrochemical detection. A marked reduction in 5-HT levels was found in male and female patients with major depressive disorder, as compared to controls, but not in dysthymic disorder. These modifications may constitute biochemical changes suggestive of major depressive disorders; they could not be attributed to chronic antidepressant treatment.

Adult↗

Rapid liquid chromatographic determination of 5-hydroxyindoles and dihydroxyphenylacetic acid in cerebrospinal fluid of the rat.

A stainless steel guide was implanted in the anterior third ventricle of the anesthetized rat and an internal needle shorter than the guide was used to continuously collect cerebrospinal fluid (CSF) at a constant outflow of 1 microliter/min. Five microliter samples were injected directly into a liquid chromatographic column. The mobile phase was adjusted for selective separation of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindolacetic acid (5-HIAA). Electrochemical detection with a limit of 0.05 pmol was used, 5-HTP and 5-HT concentrations were in the 10(-8) M range in controls while DOPAC and 5-HIAA were in the 10(-7) and 10(-6) M range. Brain aromatic amino acid decarboxylase inhibition with high doses of benserazide corresponded to an increased CSF level of 5-HTP. Monoamine oxidase inhibition with tranylcypromine resulted in a diminution of DOPAC and 5-HIAA. L-Tryptophan loading associated with monoamine oxidase inhibition induced an increase in CSF level of serotonin. These pharmacologically induced changes in serotonin and dopamine metabolite levels exemplify the usefulness of these CSF determinations as indices of brain function.

3,4-Dihydroxyphenylacetic Acid↗

[Characteristics of membrane and plasma proteins in the spontaneously hypertensive rat].

The red blood cell membrane proteins and plasma proteins of normal and spontaneous hypertensive Rats were studied by uni- and bidimentional polyacrylamide gel electrophoresis. The amount of band 3 was observed to be significantly reduced in the red blood cell membrane of spontaneously hypertensive Rats. Plasma from these Rats contained two additional heatstable proteins, characterized by a molecular weight of 16,000 dalton and isoelectric points of 4.7 and 5.1. These changes may constitute biochemical changes genetically associated with hypertension.

Animals↗