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Biomedical subjects

M A Devynck

Publications and source records attributed to M A Devynck.

At least 109 records · Page 6Linked to original sources
PubMed1987

Platelet cytosolic free Ca2+ concentration and serotonin (5-HT) content in essential hypertension.

Cytosolic free [Ca2+] and serotonin (5-HT) content were measured in platelets from 22 untreated hypertensive patients and 16 normotensive subjects. In hypertensive patients, cytosolic free [Ca2+] was significantly higher (239 +/- 13 nmol/l versus 186 +/- 7 nmol/l, n = 22 and 16, P less than 0.01) and 5-HT content was significantly lower than those measured in cells from control subjects (3.22 +/- 0.26 versus 4.99 +/- 0.38 X 10(-7) mol/10(11) cells, n = 22 and 16, P less than 0.001). These two parameters were closely correlated (r = -0.565, n = 38, P less than 0.001). These two concomitant changes in platelet characteristics might result from a common cause, such as cell membrane alterations. As ritanserine, a specific 5-HT2 receptor antagonist, did not modify the cytosolic free [Ca2+], a higher stimulation of 5-HT2 receptors is not likely to be responsible for the enhanced free Ca2+ levels.

Adult↗
PubMed1987

Relationship between platelet cytosolic free calcium concentration and plasma renin activity.

1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization.

Blood Platelets↗
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↗
PubMed1987

Platelet cytosolic free Ca2+ concentration and plasma cholesterol in untreated hypertensives.

It has been proposed that plasma cholesterol, a major risk factor for atherosclerosis, may modify cellular Ca2+. In particular, higher membrane cholesterol contents induce higher Ca2+ influx and decrease the activity of the Ca2+ pumps. Cellular Ca2+ may also control the number of accessible low density lipoprotein receptors. We investigated the question of whether plasma cholesterol influences cellular Ca2+ metabolism, by analysing the cytosolic free Ca2+ concentration [( Ca2+]i) in unstimulated platelets from 61 untreated hypertensive patients [systolic and diastolic arterial pressure: 157 +/- 3/95 +/- 2 mmHg (mean +/- s.e.m.), respectively, age 41.8 +/- 1.7 years, body mass index 24.7 +/- 0.6 kg/m2]. The subjects' plasma total cholesterol (5.5 +/- 0.5 mmol/l) and platelet [Ca2+]i concentration (228 +/- 7 nmol/l) were positively correlated (r = 0.375, P less than 0.003). This correlation persisted at constant age, arterial pressure or body mass index. Platelet [Ca2+]i tended to increase with plasma low-density lipoprotein concentration (n = 21, P = 0.01), and to decrease with the ratio of high-density lipoprotein cholesterol to total cholesterol (n = 21, P = 0.08). The observation that in normocholesterolaemic hypertensive patients [Ca2+]i concentration in unstimulated platelets was correlated with plasma cholesterol suggests that cell activation may be modulated by membrane fluidity or that cholesterol metabolism is influenced by cell Ca2+.

Adult↗
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

Increased platelet cytosolic free calcium concentration in essential hypertension.

Cytosolic free calcium concentration [Ca2+] was studied in platelets of hypertensive patients with the use of the fluorescent indicator Quin 2/AM. Cytosolic free Ca2+ was significantly higher in platelets of hypertensive patients than in those of normotensive subjects (241 +/- 9 versus 192 +/- 7 nmol/l, n = 58 and 57, respectively P less than 0.001). When all 115 subjects were included, there was a significant correlation between cytosolic free Ca2+ and systolic or diastolic blood pressure (r = 0.262, P less than 0.0025 and r = 0.251, P less than 0.0025, respectively). Intracellular Quin 2 concentration was measured to evaluate the formaldehyde production (a product of Quin 2/AM hydrolysis which has been described as reducing the adenosine triphosphate (ATP) production). The Quin 2 concentrations in platelets of the two groups of subjects were observed to be similar (0.41 +/- 0.03 versus 0.38 +/- 0.03 mmol/l, n = 8 and 7 for hypertensives and normotensives, respectively). The effects of prostaglandin E1 (PGE1), an adenylate cyclase stimulator, on cytosolic free Ca2+ were studied. The presence of 10(-7) mol/l PGE1 lowered the Ca2+ in platelets of hypertensive patients only, suppressing the difference between the two groups.

Adolescent↗
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

Chemical and clinical studies of endogenous digitalis-like factor in hypertension.

Endogenous digitalis-like factor (endalin) was investigated by measuring the ability of rat and human plasma and urine to inhibit [3H]ouabain-specific binding, digoxin-antidigoxin antibodies interaction, and renal Na+, K+-ATPase activity. Endalin was detected in plasma (and urine) of one third of 112 patients with sustained and moderate hypertension (Na+ intake = 110 mmol/l). Endalin tended to be increased in the more pronounced hypertensives. No correlation with any other clinical and biological parameter could be detected. An activity to inhibit Na+, K+-ATPase was also detected in the rat after acute and chronic Na+ loading, in reduced renal mass-type hypertension and in SHRs as compared to WKY rats. Comparison of the plasma and urine inhibitory effects in the different tests revealed some chemical heterogeneity. However, a compound possessing the biochemical and pharmacological characteristics of digitaline was extracted from human urine. Chromatographic and spectral analysis of about 1,000 liters revealed a compound with apparent chemical homogeneity, molecular weight around 500, devoid of peptidic bound and of aliphatic structure.

Adult↗
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

Calmodulin abolishes the changes in Ca2+ binding and transport by heart sarcolemmal membranes of spontaneously hypertensive rats.

Both Ca2+ transport and binding properties of heart sarcolemmal membranes are altered in spontaneously hypertensive rats (SHR) when compared to their normotensive controls (WKY). The effects of calmodulin on these two processes were studied at free calcium concentrations presumed to be the physiological levels in the cytosol. At a calcium concentration of 2.10(-8)M, calmodulin did not significantly modify either binding or ATP-dependent accumulation of calcium by membranes of both origins. In contrast, at a free calcium concentration of 4.10(-7)M, calmodulin enhanced the calcium binding to SHR membranes and the ATP-dependent calcium transport by SHR and WKY membranes. Differences in calcium binding and ATP-dependent accumulation between the two substrains were suppressed in presence of calmodulin. These data demonstrate that modifications in calcium handling by SHR cardiac plasma membranes might be due to altered intracellular content or function of calmodulin in SHR.

Adenosine Triphosphate↗
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↗