Biomedical subjects

M G Pernollet

Publications and source records attributed to M G Pernollet.

At least 37 records · Page 2Linked to original sources

PubMed1988

Correlations between plasma levels of an endogenous digitalis-like substance and haemodynamic parameters measured during cardiac catheterization.

It has been postulated that one or more plasma digitalis-like compounds may play an important role in body fluid regulation and in essential hypertension, although very little is known about their possible role in general haemodynamics. We therefore measured plasma inhibition of human kidney Na+,K+-ATPase and plasma cross-reactivity with digoxin antibodies in 11 normotensive cardiopathic subjects admitted to our clinic for heart catheterization. Possible correlations with haemodynamic parameters were studied. Plasma digoxin-like activity correlated directly with left atrial pressure and with pulmonary circulation data. The ability of the plasma to inhibit Na+,K+-ATPase showed an inverse correlation with cardiac output and cardiac index. No correlations were found with any of the other parameters measured, notably systemic resistance, blood pressure and natriuresis. These findings suggest the presence of more than one substance sharing chemical properties with digitalis: (1) a substance cross-reacting with digoxin antibodies and dependent on pulmonary vascular congestion; and (2) a substance capable of inhibiting the Na+-K+ pump and present in large amounts in heart diseases with a reduced cardiac index.

Adult↗

PubMed1988

Antihypertensive effect of canrenone in a model where endogenous ouabain-like factors are present.

The effect of canrenone, an antialdosterone and partial ouabain-agonist drug, was studied in rats that developed volume expansion and hypertension after renal mass reduction and excess Na+ intake (RRM-salt). The RRM-salt was characterized by: (1) increased endogenous "digitalis-like" compounds in plasma [cross reactivity with digoxin-antibodies (57.5 +/- 5.0 vs. 42.1 +/- 3.8 pg/ml, p less than 0.02); inhibition of kidney Na+, K+-ATPase activity (135 +/- 5 vs. 154 +/- 5 mumol/mg/h, p less than 0.01); and inhibition of Na+ extrusion from normal erythrocytes (5.96 +/- 0.40 vs. 7.68 +/- 0.34 mmol/L cells/h, p less than 0.01)]; (2) reduced Na+, K+-pump activity (7.34 +/- 0.29 vs. 10.88 +/- 0.41 mmol/L cells/h, p less than 0.001) and increased Na+ content (4.66 +/- .08 vs. 4.16 +/- 0.11 mmol/L cells, p less than 0.01) in erythrocytes; and (3) low plasma renin activity (2.1 +/- 0.9 vs. 12.6 +/- 1.6 ng/ml/h). Ninety minutes after the administration to RRM-salt of a single oral dose of 60 mg/kg of canrenone, the systolic blood pressure decreased by 36 +/- 4 mm Hg (mean +/- SEM). Chronic canrenone administration (60 mg/kg/day) resulted in a marked antihypertensive effect associated to a correction of volume expansion, a decrease in endogenous "digitalis-like" compounds, and a partial recovery of Na+, K+-pump activity and Na+ content in erythrocytes. Our results suggest that the antihypertensive effect in RRM-salt rats results, at least in part, from antagonism with endogenous "digitalis-like" compounds.

Animals↗

PubMed1988

Endogenous digitalislike circulating substances in spontaneously hypertensive rats.

Circulating digitalislike compounds have been proposed to be involved in some Na+-dependent types of experimental hypertension and in human essential hypertension. The level of circulating Na+-K+ pump inhibitor(s) was investigated in the spontaneously hypertensive rat of the Okamoto strain (SHR), its normotensive control, Wistar-Kyoto rat (WKY), and the regular Wistar rat using the following criteria: the ability of whole plasma to inhibit the total active Na+ efflux from Wistar rat erythrocytes and to cross-react with digoxin antibodies and the ability of plasma extracts to inhibit Na+,K+-adenosine triphosphatase (ATPase) activity of membranes from rat kidney. SHR plasma inhibited the net Na+ efflux from Wistar erythrocytes by up to 27% compared with WKY or Wistar plasma. For a given number of cells, the inhibition increased with the amount of available plasma. Cross-reactivity with digoxin antibodies was twice as high in SHR as in WKY or Wistar plasma. It was already enhanced in 3- to 4-week-old rats. Plasma extracts from SHR significantly inhibited Na+,K+-ATPase activity when compared with WKY extracts (75.6 +/- 2.6 vs 89.3 +/- 2.4 mumol Pi/mg/hr; p less than 0.01) but did not differ from Wistar plasma extracts. These results strongly suggest that circulating digitalislike compound(s) are present in elevated amounts in SHR as early as 3 to 4 weeks of age, but their exact participation in blood pressure elevation or maintenance remains to be clarified.

Animals↗

PubMed1988

[Variations in the plasma concentrations of atrial natriuretic factor and endogenous digitalis compounds during acute volume expansion in the conscious rat].

Atrial natriuretic peptide (ANP) and Na+ pump inhibitor (digitalis-like substance, DLS) have both been proposed to participate in body sodium and water homeostasis. Plasma levels and ANP and DLS have been reported to be increased in physiological or pathological states characterized by volume expansion. In order to investigate possible mutual relationships, their concentrations were measured in parallel during acute volume expansion by injection of 25 ml/kg isotonic NaCl (A) or blood (B) in the conscious rat. ANP was measured by radioimmunoassay and DLS by inhibition of renal Na+, K+-ATPase activity and digoxin-like immunoreactivity (DLI). Five minutes after injection, plasma ANP increased to reach 700 pg/ml (A, n = 21) or 1,500 pg/ml (B, n = 5) but the ability of plasma extracts to inhibit the renal Na+, K+-ATPase activity was unchanged (16.6 +/- 2.5 vs 16.9 +/- 2.0 p. 100, A, n = 8 and 6). Digoxin-like immunoreactivity was slightly lowered after NaCl injection from (74.4 +/- 6.2 to 65.4 +/- 5.1 pg/ml, n = 21) and unchanged after blood injection (79.0 +/- 3.4 vs 81.2 +/- 5.0 pg/ml, n = 5). Plasma ANP concentrations then decreased and had returned to preinjection values before 30 (A) or 90 (B) minutes, whereas the capacity of plasma to inhibit the Na+, K+-ATPase tended to increase (25.9 +/- 4.7 p. 100 at 3 hours after injection, n = 12 compared to 17.6 +/- 1.6 p. 100, n = 20) and DLI remains stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Plasma levels of digitalis-like substance in Nigerians with essential hypertension.

A plasma Na+-K+ ATPase inhibitor, which is estimated by a technique in which it competes with ouabain for binding on red cells, was measured in three groups of individuals: (a) normotensive subjects without a family history of hypertension, (b) normotensive subjects with a family history of hypertension, (c) untreated essential hypertensive subjects. The mean value of the inhibitor in group (b) subjects was significantly higher than the mean value in group (a). The mean value in group (c) subjects was also significantly higher than in group (a) subjects. However, the means of the values in groups (b) and (c) were not significantly different. There was a significant positive correlation between the levels of the inhibitor and the urinary Na+ excretion in all subjects. However, there was no correlation between the inhibitor levels and mean arterial pressure. The relevance of these results to the pathophysiology of hypertension in the black African subject is discussed.

Adult↗

PubMed1987

Evidence of an endogenous digitalis-like factor in the plasma of patients with acromegaly.

Evidence suggests that plasma-volume expansion leads to the release of a digitalis-like factor, which is thought to act on the renal tubular cells and cause natriuresis. We postulated that this factor might be present in patients with acromegaly (in whom plasma volume is elevated) and might return to normal levels when the disease was treated successfully. We measured the ability of plasma extracts from patients with acromegaly to inhibit the binding of ouabain to the sodium pump in normal red cells and to inhibit the enzymatic activity (sodium-potassium-ATPase) of the sodium pump in membrane preparations from normal kidneys. In 21 patients with active acromegaly, the mean (+/- SE) level of ouabain-binding inhibition (1.56 +/- 0.38) was higher (P less than 0.01) than that in either 11 successfully treated patients (0.18 +/- 0.05) or in 27 normal controls (0.19 +/- 0.03). The inhibition of sodium-potassium-ATPase activity by plasma was also greater in patients with active acromegaly (38.1 +/- 6.8 percent) than in successfully treated patients (18.4 +/- 5.6 percent, P less than 0.05) or controls (21.1 +/- 2.7 percent, P less than 0.05). Significant correlations were found between plasma volume and ouabain-binding inhibition in 23 patients (r = 0.72, P less than 0.01) and sodium-potassium-ATPase inhibition in 19 patients (r = 0.62, P less than 0.01). Pituitary adenomectomy decreased plasma volume and the inhibition by plasma of ouabain binding. We conclude that an endogenous digitalis-like factor is present in the plasma of patients with chronic volume expansion due to acromegaly. These results are consistent with the hypothesis that this natriuretic factor may have a physiologic role in water and sodium homeostasis.

Acromegaly↗

PubMed1987

Endogenous digitalis-like compounds in essential and experimental hypertension.

The hypothesis that endogenous digitalis-like compounds might participate in body sodium and water homeostasis have led us to investigate the presence in plasma of compounds interacting with digoxin antibodies in man and rats. The apparent levels of digoxin-equivalents in plasma of control subjects (n = 21) and patients with essential hypertension (n = 48) or end-stage renal failure (n = 13) were 24.7 +/- 3.2, 34.4 +/- 4.4 and 98.7 +/- 17.4 pg/ml, p less than 0.05 and p less than 0.01 respectively. Positive correlations were observed between systolic and diastolic blood pressure and the apparent immunoreactivity of plasma. No relationship was found with the renal Na+ excretion or the plasma renin activity. The apparent digoxin-like immunoreactivity of the plasma was correlated with its ability to inhibit ouabain binding to the erythrocyte Na+ pump and to reduce the renal Na+,K+-ATPase activity. In rats with experimental hypertension, the plasma cross-reactivity with antidigoxin antibodies was also enhanced when compared to control rats (71.6 +/- 10.2 pg/ml, n = 12 and 57.3 +/- 5.0 pg/ml, n = 33 in Na+ loaded rats and in rats with reduced renal mass respectively compared to 43.4 +/- 3.7 pg/ml, n = 36, p less than 0.05). In spontaneously hypertensive rats (SHR), the apparent levels of digoxin- equivalents were higher than that of age-matched WKY normotensive rats. This increase was already present in prehypertensive SHR (3 week-old) (105.8 +/- 12.4 vs 40.0 +/- 6.5 pg/ml, n = 9 and 8, p less than 0.001) and persisted after hypertension has developed (134 +/- 12.6 vs 85 +/- 7.9 pg/ml, n = 7 and 8, p less than 0.005 in 30 week-old rats). The apparent affinity of the erythrocyte Na+,K+ cotransport for intracellular Na+ and the maximal rate of the Na+ pump were correlated with the plasma digoxin-like levels. These results confirm the presence in plasma of compounds possessing some of the functional and structural properties of cardioactive steroids, associated with a rise in blood pressure.

Adult↗

PubMed1987

Changes in platelet free Ca2+ concentration after chronic digoxin treatment.

Cell Na+ and Ca2+ concentrations control each other by various mechanisms. In excitable cells from various origins, Ca2+ extrusion from the cell and its entry are dependent for a large part on the activity of the Na+, Ca2+-countertransport system. Cytosolic free Ca2+ concentration is also controlled by the Na+-H+ exchange activity. To analyze the changes in cytosolic Ca2+ concentration accompanying the reduction of the membrane Na+ gradient, cytosolic free Ca2+ concentration ([Ca2+]i) was measured by fluorescent dyes in platelets and erythrocytes from healthy subjects, before and during digoxin treatment (0.25 mg/day for 6 days). [Ca2+]i was increased in platelets from 169 +/- 30 to 321 +/- 61 nmol/l (n = 7, P less than 0.02) and unchanged in erythrocytes (121 +/- 6 and 104 +/- 7 nmol/l). This increase in platelet [Ca2+]i was not accompanied by a change in serotonin content (5.43 +/- 0.67 vs 5.49 +/- 0.61 10(-7) mol per 10(11) cells) and could not be reproduced by in vitro addition of 10(-4) mol/l ouabain (198 +/- 33 vs 186 +/- 73 nmol/l). The enhanced [Ca2+]i in platelets is thus not a short-term consequence of a reduced membrane Na+ gradient, but reflects either the overload of intracellular Ca2+ stores or an enhanced in vivo stimulation by hormones or neurotransmitters.

Adult↗

PubMed1987

[Genetic hypertension in the SHR rat and circulating digitalis compounds].

Circulating digitalis-like compounds have been found elevated in some experimental sodium--and volume--dependent hypertensions, as well as in human essential hypertension. As few studies have been undertaken to assess their enhancement in the genetic hypertension of Okamoto (SHR) we have investigated their presence in plasma using 4 criteria: their apparent immunoreactivity with antidigoxin antibodies, their competition with tritiated ouabain binding to the sodium pump of human red blood cells,-their ability to inhibit the Na+, K+ ATPase activity of rat kidney membranes, and the Na+ fluxes from rat red blood cells. When compared to ordinary Wistar (W) and Wistar Kyoto rats (WKY), SHR exhibited a markedly enhanced apparent immunoreactivity with antidigoxin-antibodies (138 +/- 8; 59 +/- 3; 61 +/- 4 pg/ml, n = 15, 6 et 15, p less than 0.001, and p less than 0.001 respectively). The inhibition of ouabain binding by plasma extracts of the three strains did not differ (10.3 +/- 1.6, 9.9 +/- 1.7 and 12.9 +/- 1.4 ng/ml, n = 9, 18 and 14 respectively). When compared to WKY, SHR plasma extracts inhibited the renal Na+, K+ ATPase activity (75.6 +/- 2.6 vs 89.3 +/- 2.4 mumoles Pi . mg-1 . h-1, n = 11 and 10, p less than 0.01, respectively). When incubated in SHR plasma for one hour, net sodium effluxes from Wistar erythrocytes were inhibited compared to that measured in the presence of W or WKY plasma: (5.91 +/- 0.20 vs 7.68 +/- 0.25 and 7.52 +/- 0.15 mmol/l cells, n = 5, 3 and 5, p less than 0.001, and p less than 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

[Endogenous digitalis compounds and adrenal gland activity].

Endogenous inhibitors of the Na+,K+-pump have been postulated to participate in Na+ and water homeostasis. When present in high amounts, they have been proposed to induce a rise in blood pressure. There is no general agreement concerning their chemical structure and their possible tissue origin has not been well defined. In an attempt to identify a tissue source, (i) the digitalis-like contents of various organs (cross reactivity with digoxin antibodies and inhibition of ouabain binding to the Na+ pump) were determined and (ii) the circulating digitalis-like activity was analyzed under various conditions known to alter the activity of the putative source organs. High levels of digitalis-like compounds were present in the adrenal and pituitary glands (4.1 +/- 0.1, n = 15 and 3.7 +/- 0.4, n = 13 ng digoxin equivalents/g) or 328 +/- 66, n = 6 and 460 +/- 76, n = 6 ng ouabain equivalents/g) respectively. Much lower levels were found in heart, kidney, brain and hypothalamus. Plasma digitalis-like activity was measured in 5 groups of rats: control, ACTH treated, hypophysectomised, and in DOCA-salt treated animals with and without bilateral adrenalectomy. Changes in the plasma digitalis-like activity measured by the crossreactivity with anti-digoxin antibodies or by the inhibition of ouabain binding followed the same pattern. When compared to the control values, the plasma digitalis-like activity was partially decreased after hypophysectomy, markedly decreased after adrenalectomy and enhanced in ACTH-treated animals. These results suggest that the pituitary-adrenal axis plays a major role in the control of the circulating "digitalis-like" activity.

Adrenal Glands↗

PubMed1986

High sodium diet and circulating digitalis-like compound in the rat.

The effects of a high salt diet (8% NaCl) on blood pressure and intra-erythrocytic Na+ content were studied in Wistar rats. The ability of the plasma to inhibit the renal Na+,K+-ATPase activity and to cross-react with digoxin antibodies was also investigated. After 1 week, neither systolic blood pressure nor intra-erythrocytic Na+ content were modified, but plasma extracts slightly inhibited renal Na+,K+-ATPase (70.9 +/- 1.7 versus 76.3 +/- 2.1 mumol Pi/mg per h, P = 0.05). After 2 weeks, the plasma inhibitory activity, systolic blood pressure and intra-erythrocytic Na+ content were higher than corresponding values in control animals (65.5 +/- 1.6 versus 79.1 +/- 2.8 mol Pi/mg per h, P less than 0.001; 132 +/- 2 versus 114 +/- 4 mmHg, P less than 0.001, and 4.95 +/- 0.32 versus 3.81 +/- 0.36 mmol/l cells, P less than 0.05, respectively). After 3 months, the plasma digoxin-like immunoreactivity and its ability to inhibit the Na+ pump were elevated (68.7 +/- 7.9 versus 48.2 +/- 5.4 pg/ml, P less than 0.02; 57.8 +/- 1.8 versus 72.9 +/- 1.8 mumol Pi/mg per h, P less than 0.001, respectively) whereas intra-erythrocytic Na+ content had returned to control levels. The results demonstrated that this high salt intake led to simultaneous increases in systolic blood pressure and in the activity of a digitalis-like compound present in plasma. The inhibition of Na+,K+-ATPase was correlated with systolic blood pressure and digoxin-like immunoreactivity (r = 0.569, n = 76, P less than 0.001 and r = 0.414, n = 34, P less than 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Active Na+ and Ca+ transport, Na+-Ca2+ exchange, and intracellular Na+ and Ca2+ content in young spontaneously hypertensive rats.

The activity of Na+-Ca+-exchange and ATP-dependent Na+ and Ca2+ transport by heart sarcolemmal membranes from male 3-4-week-old spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) were compared. Differences in active Ca2+ and Na+ transport between the two substrains were suppressed by addition of exogenous calmodulin. Calmodulin was active only in the presence of Ca2+. The rate of the Na+-dependent Ca2+ efflux, reflecting the activity of the Na+-Ca2+ exchange, was significantly higher in SHR than in WKY vesicles. An alteration of the intracellular calmodulin activity or content might thus be responsible for the modifications in Ca2+ handling, and limit the activity of the Na+ pump in SHR membranes. The platelet cytosolic free Ca2+ concentration of young SHR and WKY was measured by using the fluorescent indicator Quin-2/AM. In the absence or presence of added external Ca2+, no difference in the intracellular concentration of Ca2+ was observed between platelets of either origin. The intraerythrocytic sodium content, measured by flame spectrophotometry, was similar in SHR and WKY. This study, performed before the onset of hypertension, shows that membrane mechanisms controlling the intracellular ion content were already modified, whereas the resulting intracellular concentrations remained within the normal range.

Animals↗

PubMed1986

Plasma digitalislike activity in essential hypertension or end-stage renal disease.

Plasma extracts from 119 subjects showed a digitalislike activity, as evidenced by the ability of these extracts to inhibit ouabain binding to the Na+-K+ pump. High levels of the digitalislike compound were found in 18 of 54 untreated hypertensive subjects, 7 of 21 normotensive subjects with a family history of hypertension, and 10 of 14 patients with end-stage renal failure. Dialysis significantly reduced the activity of this compound. These results suggest 1) that endogenous digitalislike factor is not directly linked to hypertension but rather is related to sodium balance and 2) that it neither originates nor is activated by renal tissue, as it was present in four of six anephric patients.

Adult↗

PubMed1986

Structural and functional alterations of the cell membrane in the prehypertensive rat of the Okamoto Aoki strain.

Plasma membrane properties of 3 to 4-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were investigated in both excitable cells, i.e. cardiomyocytes and platelets, and non-excitable cells, i.e. erythrocytes. Cardiac sarcolemma from SHR exhibited: lowered capacity of high-affinity Ca2+-binding sites; higher Ca2+ pump activity; higher Na+K+-ATPase activity due to increased density of Na+ pump units; suppression of the above three effects by the Ca2+-calmodulin complex, and increased Na+Ca2+ exchange. No difference in platelet cytosolic free Ca2+ concentration was observed between SHR and WKY. In both substrains, erythrocyte intracellular Na+ content was similar in spite of reduced Na+ and K+ net fluxes. Isolated membranes from SHR erythrocytes were also characterized by: lowered phosphoinositide turnover; decreased ATP-dependent Ca2+-transport, and lowered capacity of high affinity Ca2+-binding sites. Structural alterations detected by fluorescence polarization of diphenylhexatriene were observed in SHR cardiac sarcolemma, erythrocyte and brain synaptosomal membranes. Membrane organization and activity of transport systems controlling the intracellular Na+ and Ca2+ level were thus already modified in the prehypertensive animals whereas the resulting intracellular ion contents were still unaltered.

Animals↗

PubMed1986

[Compounds of the digoxin type in essential and experimental hypertension].

The prescription of cardiac glycosides is usually controlled by immunological measurement of their plasma concentration. The observation of false positive digoxin measurements in patients free of this drug and the hypothesis that endogenous digitalis-like compounds might participate in body sodium and water homeostasis have led us to investigate the presence in plasma of compounds interacting with digoxin-antibodies under various physiological and pathological conditions in man and rats. The apparent levels of digoxin-equivalents in plasma of healthy control subjects (n = 21) and patients with essential hypertension (n = 48) or end-stage renal failure (n = 13) were 24.7 +/- 3.2, 34.4 +/- 4.4 and 98.7 +/- 17.4 pg/ml, p less than 0.05 and p less than 0.01 respectively. Positive correlations were observed between systolic and diastolic blood pressure and the apparent immunoreactivity of either whole or deproteinized plasma, in particular when only male subjects were considered. No relationship was found with the renal Na+ excretion or the plasma renin activity and the apparent immunoreactivity of the plasma. Its levels were however correlated with its ability to inhibit ouabain binding to the erythrocyte Na+ pump and to its capacity to reduce the renal Na+, K+-ATPase activity. In rats with experimental hypertension, induced by chronic excess salt intake either alone or associated with reduced renal mass, the cross reactivity with antidigoxin antibodies was also enhanced when compared to control rats (71.6 +/- 10.2 pg/ml, n = 12 and 57.3 +/- 5.0 pg/ml, n = 33 respectively compared to 43.4 +/- 3.7 pg/ml, n = 36, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

PubMed1986

[Canrenone: an effective antihypertensive in an experimental model of hypertension in which the active transport of sodium is diminished].

Recent studies in essential hypertensive patients and rats with genetic hypertension strongly suggested that the development of primary hypertension results from a transient and chronic "cascade" of events; I) excess Na+ intake, II) secretion of natriuretic factors, III) abnormal cell Na+ homeostasis in the vascular wall, due to the presence of inherited and induced abnormalities in different Na+ transport system and IV) increase in cytosolic free Ca2+ content and sympathetic drive. In vitro studies have previously shown that canrenone, an antihypertensive antialdosterone drug, behaves like a partial agonist at the digitalis-receptor site of the Na+, K+-pump. In particular, it has been shown that canrenone counterbalances the increases in internal Na+ and cytosolic free Ca2+ contents induced by ouabain in cultured smooth muscle cells. We thus investigated the effect of canrenone administration in a model of experimental hypertension with increased endogenous "ouabain-like" factors (rats with reduced renal mass under excess Na+ intake: RRM-salt rats). Results presented here confirm that RRM-salt rats exhibit: volume expansion, strongly decreased plasma renin activity, increased endogenous "ouabain-like" factors and (IV) decreased Na+, K+-pump activity and increased Na+ content in erythrocytes. In addition, we found that canrenone is antihypertensive in this model and this is associated with a tendency to normalize volume expansion, plasma levels of endogenous "ouabain-like" factors, Na+, K+-pump activity and Na+ content in erythrocytes. In conclusion, our results suggest that administration of canrenone to RRM-salt rats may induce a lowering of blood pressure by antagonism with endogenous "ouabain-like" factors at the vascular wall.

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↗