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Biomedical subjects

M Mazeaud

Publications and source records attributed to M Mazeaud.

10 recordsLinked to original sources
PubMed1993

Acute membrane effects of trimetazidine in human platelets.

The mechanisms by which trimetazidine (1-[2,3,4-trimethoxybenzyl]-piperazine) exerts its cytoprotective action have not been identified. This study was designed to investigate in human platelets and erythrocyte ghosts a possible perturbation of membrane dynamics by trimetazidine. Its effects on the steady-state anisotropies of two fluorescent probes, trimethylamino-diphenyl-hexatriene (TMA-DPH) and diphenylhexatriene (DPH) were compared. The effects on the aggregatory responses to collagen and ADP, and on platelet cAMP content were also investigated. In platelets, trimetazidine dose-dependently raised TMA-DPH anisotropy but not that of DPH. It reduced cAMP content (in the presence of Ro 15-2041, a phosphodiesterase inhibitor) and the aggregation responses to collagen and ADP. This suggests that trimetazidine decreases the 'fluidity' of the outer part of the plasma membrane, the adenylyl cyclase activity and some steps involved in platelet activation. In erythrocyte ghosts, the fluorescence anisotropy of TMA-DPH was not modified by trimetazidine. The membrane effects reported here could participate in the protection of cell metabolism afforded by a long-term treatment with trimetazidine.

Adenosine Diphosphate↗
PubMed1993

Plasma lipids and platelet membrane fluidity in essential hypertension.

Essential hypertension is often associated with high levels of plasma cholesterol or triglycerides. The relationships between plasma lipids and platelet lipids, membrane fluidity and functions in untreated hypertensive patients were investigated by measuring the fluorescence anisotropies of two fluorescent dyes (DPH and its cationic derivative, TMA-DPH, with different subcellular localization), cytosolic Ca2+ and pH, cyclic AMP content and aggregation to ADP and collagen. Hypercholesterolemia was found to be accompanied by a rise in platelet cholesterol content without changes in TMA-DPH or DPH anisotropies whereas hypertriglyceridemia was associated with a decreased cholesterol to phospholipid molar ratio, a decreased DPH anisotropy and a tendency of the cytosol to alkalinize. These results point out the differences between the effects of an acute cholesterol load and those of chronic hypercholesterolemia on platelet membrane microviscosity and aggregation. They demonstrate a strong association between plasma triglyceride levels and platelet membrane structure.

Adult↗
PubMed1991

Acute sodium-dependent changes in membrane dynamic properties.

Na+ ions, which can play a pathogenic role in the development of high blood pressure, have been reported to regulate membrane enzymatic activities, receptor-ligand interaction and coupling of G-protein receptors to their effectors. This study was designed to investigate the in vitro effects of Na+ ions on membrane dynamic properties. The fluorescence anisotropy values of TMA-DPH (trimethylamino-diphenylhexatriene, probe selectively incorporated into the outer leaflet of the plasma membrane) was evaluated in platelets and erythrocytes of sodium-dependent hypertension-prone and -resistant rats of the Sabra Strain. Whereas no difference was observed between the 2 strains, TMA-DPH anisotropy was found to be strongly influenced in platelets by external Na+ ions. In the absence of external Na+, TMA-DPH anisotropy increased in human and rat platelets. In contrast, Na+ ions did not affect the anisotropy when the probe was inserted into erythrocyte ghosts. This indicates that Na+ ions can acutely regulate order parameter and microviscosity of platelet plasma membrane in the regions explored by the probe.

Animals↗
PubMed1990

Endogenous inhibitors of the Na+, K(+)-pump and platelet Ca2+ handling in hypertension.

Inhibition of the Na(+)-K+ pump by digitalis compounds has been reported to increase intracellular Na+ and Ca2+ concentrations and to stimulate Na(+)-H+ exchange. The activity of endogenous digitalis-like compounds, proposed to promote natriuresis and to raise blood pressure, has been found to be increased in volume expansion and hypertension. The enhanced cytosolic [Ca2+] present in platelets from hypertensive patients may thus originate from inhibition of the Na(+)-K+ pump by endogenous inhibitors, enhanced mobilization of internal Ca2+ stores due to phospholipase C activation and/or structural membrane defects. In unstimulated platelets from essential hypertensives, the increase in [Ca2+]i depends on external Ca2+, thereby underlining the importance of Ca2+ influx. The observation that [Ca2+]i was also enhanced in erythrocytes (p = 0.03) demonstrates that intracellular stores are not required for this rise. Plasma digitalis-like activity was positively correlated with platelet [Ca2+]i (inhibition of renal Na+,K(+)-ATPase, competition with ouabain binding, p less than 0.01). Platelet [Ca2+]i also rose during chronic digoxin administration (p less than 0.02) but not after acute in vitro ouabain treatment. The alkalinisation of platelet cytosol (p = 0.005) also agrees with the stimulation of the Na(+)-H(+)-exchange. In conclusion, these results are compatible with a participation of endogenous Na(+)-K+ pump inhibitors in the control of cytoplasmic [Ca2+] and cell excitability.

Adult↗
PubMed1986

The role of catecholamines in erythrocyte pH regulation and oxygen transport in rainbow trout (Salmo gairdneri) during exercise.

Rainbow trout were subjected to burst swimming to exhaustion followed by 4 h aerobic swimming at 80% critical swimming velocity. Severe physiological disturbances, including a marked plasma acidosis caused by the burst swim, were corrected during the 4 h of subsequent aerobic exercise. Erythrocytic pH and arterial oxygen content increased, even though plasma pH was reduced. We suggest that the increase in erythrocytic pH was caused by the action of elevated adrenaline and noradrenaline levels in the blood acting on beta-adrenergic receptors on the trout red blood cell, causing the cell to swell and raising intracellular pH, offsetting any effect of a reduction of plasma pH on erythrocyte pH and haemoglobin-oxygen binding. Propranolol blocked the action of catecholamines on trout erythrocytes. We conclude that catecholamines play an important role in maintaining oxygen transport to aerobic muscles, following burst swimming and the associated acidotic conditions.

Acidosis↗
PubMed1984

Adrenal dopamine-beta-hydroxylase activity in the ground squirrel Citellus citellus--effect of hibernation, arousal, and continuous light.

In the hibernating ground squirrel activity of adrenal dopamine-beta-hydroxylase was significantly lower as compared with the active animals (P less than 0.01). The highest activity of this enzyme was found in animals tested immediately after arousal from hibernation (P less than 0.01). The adrenal weight was higher in hibernating animals than in the active or aroused ones. The difference between the active and aroused animals was significant (P less than 0.01). Extremely high enzyme activity was found in the adrenals of animals exposed to continuous light for 3 weeks as compared with active animals kept in continuous darkness or with controls subjected to a regime of 12 hr light - 12 hr darkness (P less than 0.01). The weight of the adrenals in the three groups was about the same level.

Adrenal Glands↗
PubMed1982

Regional distribution of noradrenaline and dopamine-beta-hydroxylase in the brain of spontaneously hypertensive rats.

The catecholamine concentration and dopamine-beta-hydroxylase activity were determined in several nuclei of the brain of spontaneously hypertensive rats (SHR) compared with Wistar Kyoto (WKY) controls. Catecholamines were measured by using liquid chromatography coupled with electrochemical detection. The threshold of detection was 5 X 10(-14) mole. Dopamine-beta-hydroxylase (DBH) was assayed by a sensitive radioenzymatic assay using tyramine as the substrate. The limit of detection was 5 pmoles of octopamine per sample. Significantly lower noradrenaline content was observed in 4 week-old SHR in some medullary and hypothalamic areas which are involved in cardiovascular regulation. This abnormally was no longer detectable in 12 week-old rats. The changes in catecholamine levels observed in young rats were not observed during the development of deoxycorticosterone-salt hypertension and therefore probably do not represent a compensatory mechanism tending to limit the progressive rise blood pressure. No significant difference in DBH activity was observed between the young SHR and WKY in any brain region measured. The altered relationship between noradrenaline content and DBH activity observed in young SHR when compared to WKY suggests a change in noradrenergic neurones activity and/or structure which could correspond to a genetically transmitted neurochemical abnormality associated with the initiation of hypertension in the SHR.

Age Factors↗