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Biomedical subjects

G Thibault

Publications and source records attributed to G Thibault.

At least 109 records · Page 6Linked to original sources
PubMed1991

Renal glomerular endothelin receptors in rats with high-output heart failure.

Plasma immunoreactive endothelin (irET) concentration and renal glomerular ET receptors were investigated in rats with chronic high-output heart failure. Plasma irET was higher (0.67 +/- 0.03 fmol/ml vs. 0.52 +/- 0.04 fmol/ml) and the density of glomerular ET receptors lower (Bmax: 420 +/- 20 fmol/mg protein vs. 510 +/- 12 fmol/mg protein) in rats with heart failure than in controls. Our results indicate that circulating ET levels are responsive to changes in cardiovascular hemodynamics and suggest a potential role for ET as a vasoactive regulatory peptide during heart failure.

Animals↗
PubMed1991

Rat atrial secretory granules and pro-ANF processing enzyme.

We examined the possibility that rat atrial granules may contain a pro-ANF processing protease. Isolated atrial granules were lysed either by detergent, osmotic shock or sonication and incubated at 37 degrees C. Pro-ANF processing and/or degradation were followed by radioimmunoassays and Western blotting using three antibodies which are specific either to the N-terminus, the C-terminus or the processing site (98-99) of pro-ANF. Whatever the method used for the lysis of the granules, we failed to detect any production of ANF (99-126) and ANF (1-98). However, slight degradation of pro-ANF was recorded probably due to contamination by lysosomal proteases. The in vitro system was validated by addition of thrombin to lysed granules which resulted in a rapid disappearance of the immunoreactivity related to the processing site. These results suggest that the rat atrial granules do not contain any active processing enzyme unless adequate incubation conditions were not met to express its enzymatic activity. The atrial granules may not be directly involved in the maturation of pro-ANF.

Animals↗
PubMed1991

The inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on in vitro lymphocyte proliferation is associated with reduced interleukin 2 receptor expression.

The mechanisms by which vesicles of syncytiotrophoblast plasma membranes (STPM) prepared from full-term human placentas inhibit lymphocyte proliferation have been investigated. In the presence of STPM, IL-2 secretion and the expression of protein P55 (IL-2R P55) from its receptor were examined in two models of PBMC proliferation: induced by PHA in 3-day-old cultures, and induced by IL-2 in 6-day-old cultures. In the case of PHA stimulation, STPM strongly inhibited IL-2 (but not IL-1) secretion and IL-2R P55 expression at a concentration where lymphocyte proliferation was also blocked. In these conditions, the addition of excess recombinant IL-2 (rIL-2) only partially restored proliferation and IL-2R P55 expression. In addition, STPM inhibited proliferation and IL-2R P55 expression when resting PBMC were stimulated by a high concentration of rIL-2. These results suggest that STPM inhibit lymphocyte proliferation by affecting one or several events occurring in the synthesis and/or expression of IL-2R P55 by a mechanism which is at least partially independent of its inhibitory effect on IL-2 secretion. The significance of these results is discussed in the context of the survival of the fetal allograft.

Cell Membrane↗
PubMed1991

Syncytiotrophoblast plasma membrane inhibits membrane expression of activation markers on PHA-stimulated human lymphocytes.

Studies have been carried out on the effects of full-term human syncytiotrophoblast plasma membrane (STPM) preparations on the membrane expression of the lymphocyte activation markers HLA-DR, IL-2R, TfR and CD69 during PHA-induced lymphoproliferation. STPM considerably decreases the expression of both late (HLA-DR) and early (IL-2R, TfR, CD69) activation markers at doses which inhibit PHA-induced lymphoproliferation. These results favour the hypothesis that STPM inhibits a very early phase of PHA-induced lymphocyte activation.

Antigens, CD↗
PubMed1991

Abnormalities in CD4+ T lymphocyte subsets in patients with common variable immunodeficiency.

In order to investigate whether deficient immunoglobulin production in common variable immunodeficiency (CVI) patients was related to defective T cells functions, phenotype and proliferative responses to mitogen of peripheral blood mononuclear cells (PBMC) were investigated in 9 patients with CVI. The results were compared to those of 12 age- and sex-matched normal controls. The numbers of CD3+ and CD8+ T cells in the patients were not different from those in the control group, but the numbers of CD4 T cells were decreased (511 +/- 237 vs 844 +/- 247/mm3; P less than 0.01). The decrease in CD4 T cells was due to a dramatic deficiency in the CD4+ CD45RA+ subset, observed as an absolute value of blood lymphocytes (126 +/- 91 vs 384 +/- 142; P less than 0.001) and as a percentage (9.0 +/- 7.1 vs 18.8 +/- 5.0; P less than 0.01). In contrast, the CD4+ CD29+ T cell subset was not different in CVI from those in the control group. Moreover, there was a strong positive correlation between the number of percentages of CD4+ CD45RA+ blood T cells and the proliferative response of PBMC to PHA (respectively, P less than or equal to 0.02 and P = 0.05) and to Con A (P less than or equal to 0.02). The decrease of CD4+ CD45RA+ T cells could reflect an abnormality in the physiological status of T cells and could be of critical importance in the antibody deficiency.

Adolescent↗
PubMed1991

Plasma endothelin in human essential hypertension.

Plasma endothelin immunoreactivity was measured in normal controls, in mild essential hypertensive patients with no antihypertensive treatment, in moderate to severe hypertensives whose blood pressure was controlled by treatment, and in moderate to severe hypertensives whose blood pressure was not controlled by treatment. Endothelin immunoreactivity levels in plasma in the four groups were similar, but had a positive correlation with blood pressure in hypertensives although not in normotensives. The concentration in plasma of both C-terminal and N-terminal atrial natriuretic peptide also had a positive correlation with blood pressure in these hypertensive patients. We conclude that if plasma immunoreactive endothelin levels represent the result of endothelial production of endothelin, in absence of changes in catabolism of the peptide, essential hypertensive patients do not appear to have increased production of endothelin.

Adult↗
PubMed1991

A theoretical analysis of the effect of altitude on running performance.

A theoretical analysis of the effect of altitude on running performance is presented using a mathematical model we have recently described and validated (J. Appl. Physiol. 67: 453-465, 1989). This model relates the average power output available over a given running time for a given combination of anaerobic capacity, maximal aerobic power, and endurance capability. For short sprinting distances, the contribution of aerobic metabolism to the energy requirement is small and the speed sustained is high. The reduction of maximal aerobic power with altitude is, thus, negligible, whereas the reduction of aerodynamic resistance is beneficial. Accordingly the performance steadily increases with altitude (e.g., average speed for 100 m at Mexico City is 101.9% of the average speed at sea level). On the other hand, the reduction in maximal aerobic power with altitude is associated with a reduction in performance over middle and long distances (800 m to marathon). For 400 m an improvement in performance is observed up to an altitude of approximately 2,400-2,500 m (average speed approximately 101.4% of sea level speed). Beyond this altitude the reduction in air density cannot compensate for the reduction in maximal aerobic power, and the performance deteriorates. Tables of performances equivalent to the current world records for selected altitudes ranging from 0 to 4,000 m are proposed.

Aerobiosis↗
PubMed1991

Plasma atriopeptin response to prolonged cycling in humans.

The exercise-induced increase in plasma atriopeptin (ANP) has been related to exercise intensity. The independent effect of duration on the ANP response to dynamic exercise remains incompletely documented. The purpose of this study was to describe the time course of plasma ANP concentration during a 90-min cycling exercise protocol and to examine this in light of concurrent variations in plasma arginine vasopressin (AVP), aldosterone (ALD), and catecholamine (norepinephrine and epinephrine) concentrations as well as plasma renin activity (PRA). Seven male and four female healthy college students (23 +/- 2 yr) completed a prolonged exercise protocol on a cycle ergometer at an intensity of 67% of maximal O2 uptake. Venous blood was sampled through an indwelling catheter at rest, after 15, 30, 45, 60, and 90 min of exercise, and after 30 min of passive upright recovery. Results (means +/- SE) indicate an increase in ANP from rest (22 +/- 2.6 pg/ml) at 15 min of exercise (45.3 +/- 7.4 pg/ml) with a further increase at 30 min (59.4 +/- 9.8 pg/ml) and a leveling-off thereafter until completion of the exercise protocol (51.7 +/- 10.7 pg/ml). In plasma ALD and PRA, a significant increase was found from rest (ALD, 21.4 +/- 6.4 ng/dl), PRA, 2.5 +/- 0.5 ng.ml-1.h-1 after 30 min of cycling, which continued to increase until completion of the exercise (ALD 46.6 +/- 8.7 ng/dl, PRA 9.5 +/- 0.9 ng.ml-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Atrial natriuretic factor receptor subtypes in the rat central nervous system.

In this study we investigated the presence and anatomical location of atrial natriuretic factor (ANF) receptor subtypes in the rat central nervous system using in vitro autoradiographic and cross-linking techniques. 125I-ANF-(Ser99-Tyr126) served as a labeled ligand, whereas ANF-(Ser99-Tyr126) and two peptides endowed with selectivity for ANF-C receptor--namely, C-ANF (des-[Gln116-Gly120] ANF-[Asp102-Cys121]-NH2) and ANF-(Phe106-Ile113)-NH2--were used as displacing agents. Distribution studies revealed the presence of specific ANF binding sites in a number of central nervous system areas examined. C-ANF at 10(-6) M competed for 125I-ANF binding to a much lower extent than ANF in many of those structures, whereas ANF-(106-113)-NH2 at 10(-6) M did not have a significant effect on the radioligand binding except in the choroid plexus, pia-arachnoid, and olfactory bulb. Analysis of the competition curves revealed that in the choroid plexus, pia-arachnoid, olfactory bulb, subfornical organ, area postrema, and habenular nucleus, ANF interacts with its binding sites with high affinity (IC50, 0.46-0.77 nM). In contrast, C-ANF and ANF-(106-113)-NH2 competed for 125I-ANF binding with high potency (IC50, 2-16 nM) in the choroid plexus and pia-arachnoid only, where they were able to displace 60-70% of the radioligand binding. 125I-ANF cross-linking to olfactory bulb membranes resolved a specific 120-kDa band corresponding to the high molecular weight receptor but did not disclose a specifically labeled band corresponding to the low molecular mass receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Annexins V and VI: major calcium-dependent atrial secretory granule-binding proteins.

Atrial natriuretic peptide is stored by atrial myocytes in secretory granules, known as atrial specific granules, and is released from these granules by exocytosis. We have isolated a group of atrial proteins by affinity chromatography that bind to atrial specific granules in a calcium-dependent manner. The two major proteins isolated (32.5 kd and 67 kd) are calcium-binding proteins and have been identified as annexins V and VI by immunoblotting with specific antisera. The calcium dependence of their binding to atrial specific granules has been characterized in vitro and indicates that this interaction takes place at micromolar levels of calcium. In addition, the group of proteins isolated includes another calcium-binding protein of 20 kd, as well as GTP-binding proteins of 22 to 26 kd. Membrane interactions during exocytosis are presumably mediated by the interaction of specific proteins with the granule membrane. The properties of the proteins described here, and their ability to bind to atrial specific granules in a calcium-dependent manner, make them likely candidates in the search for regulatory proteins mediating atrial natriuretic peptide secretion.

Animals↗
PubMed1991

Solubilization and molecular characterization of the atrial natriuretic peptide (ANP) receptor in human platelets: comparison with ANP receptors in rat tissues.

We have previously demonstrated the presence of binding sites for atrial natriuretic peptide (ANP) in human platelets. These sites have pharmacological characteristics similar to those of rat vascular smooth muscle. They are subject to regulation by circulating levels of ANP in plasma, varying inversely with the latter after high sodium intake, in arterial hypertension and congestive heart failure. We have now solubilized these platelet receptors with the nonionic detergent Triton X-100 (0.6%). The preparations were incubated with [125I]ANP in the presence of increasing concentrations of ANP-(99-126), ANP-(101-126), ANP-(103-126), and ANP-(103-123). The order of potency of these peptides to displace [125I]ANP was similar for the solubilized and particulate receptor. Bound [125I]ANP was covalently cross-linked to the receptor with 5 mM disuccinimidyl suberate. Autoradiography of the sodium dodecyl sulfate-polyacrylamide gel showed that [125I]ANP specifically interacts with a 125-kDa membrane component, some of which may be reduced by 2% mercaptoethanol or 10 mmol/L dithiothreitol to a 70-kDa species. A small proportion of a 70-kDa peptide is also found under nonreducing conditions. The concentration of ANP-(99-126) that inhibits binding of [125I]ANP by 50% to both the 125-kDa and the 70-kDa species was 0.1 nM, while that for ANP-(103-123) was 3 nM. The internally ring-deleted analog Des(Gln116,Ser117,Gly118,Leu119,Gly120)ANP -(102-121) or C-ANP displaced with equal potency ANP binding to the high and low mol wt (Mr) bands, as also found in cultured rat vascular smooth muscle cells, but not in the mesemteric arteries these cells are derived from. In the latter, C-ANP displaced only binding from the lower Mr band. These results show that the ANP receptor in human platelets is heterogeneous. There is one nonreducible species with of 125,000 Mr, another of similar Mr containing two disulfide-linked subunits of 70,000 Mr, and, to a lesser extent, a nonreducible 70-kDa species, in agreement with findings in other tissues in experimental animals.

Amino Acid Sequence↗
PubMed1991

Effects of chlorthalidone and metoprolol alone or in combination (logroton) on blood pressure, lipids, lipoproteins and circulating plasma ANF levels in essential hypertension.

The effects of chlorthalidone (mean dose 25 mg/day), metoprolol (mean dose 200 mg/day) or their combination (logroton) on blood pressure, lipids, lipoproteins and circulating atrial natriuretic factor (ANF) were evaluated in a controlled trial of 42-week duration in 33 hypertensive patients. There was a significant reduction in mean arterial pressure after chlorthalidone and metoprolol treatments. This effect was more pronounced with the chlorthalidone/metoprolol combination (logroton). There were no significant changes in mean ANF levels after any drug regimen, although a tendency to increase was observed after six weeks of treatment with metoprolol. Both chlorthalidone and metoprolol as monotherapy increased the total triglycerides. This effect was less pronounced with logroton. During metoprolol treatment, HDL cholesterol decreased significantly, whereas VLDL-C increased. When combined drug therapy was administered, the unfavorable effects on HDL-C were partially blunted and VLDL-C returned to baseline. LDL-cholesterol did not change significantly during any drug regimen nor did the ratio of LDL-C/HDL-C. Logroton significantly increased the VLDL apo B levels in patients who had received chlorthalidone as monotherapy but had no effect in patients already treated with metoprolol. Neither treatment had a significant influence on the ratio of LDL-C/B. There were no serious adverse events reported throughout the study. It is concluded that logroton may be an effective combination therapy that produces less adverse effects on lipid and lipoprotein metabolism than chlorthalidone or metoprolol monotherapies.

Atrial Natriuretic Factor↗
PubMed1990

Immuno-electron microscopy of atrial natriuretic factor secretory pathways in atria and ventricles of control and cardiomyopathic hamsters with heart failure.

The secretory pathways of atrial natriuretic factor have been investigated in atrial and ventricular cardiocytes of control and cardiomyopathic Syrian hamsters in severe congestive heart failure with four antibodies: a monoclonal antibody (2H2) against rat synthetic atrial natriuretic factor (101-126), which is directed against region 101-103 of rat atrial natriuretic factor (99-126), and polyclonal, affinity-purified antibodies produced in rabbits against synthetic C-terminal atrial natriuretic factor (101-126), synthetic N-terminal atrial natriuretic factor (11-37) or the putative cleavage site of atrial natriuretic factor (98-99): atrial natriuretic factor (94-103). Application of the immunogold technique on thin frozen sections (immunocryoultramicrotomy) revealed an identical picture with the four antibodies. In atria of both control and cardiomyopathic hamsters where atrial natriuretic factor secretion is regulated, the atrial natriuretic factor propeptide travels, uncleaved, from the Golgi complex to immature and mature secretory granules. In ventricles of control hamsters, where secretion is constitutive, the atrial natriuretic factor propeptide travels from the Golgi complex to secretory vesicles. In the ventricles of hamsters with severe congestive heart failure, the Golgi complex is larger, secretory vesicles more abundant and a few secretory granules are present in approximately 20% of cardiocytes. Here again, the peptide travels uncleaved in all these pathways. These results reveal the pathways of secretion of atrial natriuretic factor in atrial and ventricular cardiocytes and indicate that the propeptide is not cleaved intracellularly.

Animals↗
PubMed1990

Different behaviour of the N-terminal and C-terminal fragment of proatrial natriuretic factor in plasma of healthy subjects as well as of patients with cirrhosis.

N-terminal (atrial natriuretic factor (ANF) 1-98) and C-terminal (ANF 99-126) fragments of proatrial natriuretic factor (NTA and CTA, respectively) were determined in plasma of healthy subjects adopting different postures and in patients with cirrhosis. Seven healthy subjects were investigated while seated and 30 min after assuming a horizontal position. NTA plasma concentrations increased in subjects in the horizontal position (from 734 +/- 250 (SE) fmol/ml to 902 +/- 227 fmol/ml; p less than 0.05). In contrast, CTA plasma concentrations remained unchanged (9.2 +/- 1.3 fmol/ml vs 8.9 +/- 1.6 fmol/ml). In 10 patients with cirrhosis of the liver, NTA concentrations were markedly (p less than 0.001) elevated compared to 11 healthy subjects (2334 +/- 291 fmol/ml vs 743 +/- 155 fmol/ml). However, there was no difference of CTA plasma levels between cirrhotic patients and healthy subjects (8.7 +/- 1.3 fmol/ml vs 8.2 +/- 0.9 fmol/ml). These data demonstrate changes of the plasma concentration of the N-terminal fragment of proatrial natriuretic factor by posture and in liver disease, in contrast to unchanged levels of the C-terminal fragment.

Adult↗
PubMed1990

Positive inotropic action, natriuresis and atrial natriuretic factor release induced by endothelin in the conscious rat.

Endothelin is a novel endothelium-derived vasoconstrictor peptide. We investigated its effect on atrial natriuretic factor (ANF) release and on several cardiovascular and renal parameter, since ANF release is induced via hemodynamic changes in response to angiotensin II, another vasoconstrictor peptide. Male Sprague-Dawley rats were infused intravenously for 60 min with either saline or endothelin at 10, 50 or 100 ng/kg per min and then allowed to recover for 20 min. A third group was splenectomized 24 h before infusion with 100 ng/kg per min endothelin. Mean arterial, left ventricular end-diastolic and central venous pressures (dP/dtmax), heart rate, plasma ANF-(1-98) concentration, urinary volume, urinary sodium excretion and hematocrit were evaluated. Mean arterial pressure was elevated by both medium and high endothelin doses, and with the high dose this elevation was sustained beyond the infusion period. No increases in either left ventricular end-diastolic or central venous pressures were observed at any dose level. In fact, in rats infused with 100 ng endothelin there was a progressive decline in central venous pressure and a raised hematocrit, even in the splenectomized group, suggesting a loss of plasma volume. All three dose levels elevated the dP/dtmax at different infusion times. The heart rate was not modified by any endothelin dose. Despite the decreased central venous pressure and unaltered left ventricular end-diastolic pressure, the 100 ng/kg per min endothelin infusion induced a threefold increase in plasma ANF levels; these were correlated with changes in the dP/dtmax (r = 0.49, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Dissociation between right atrial pressure and plasma atrial natriuretic factor following prolonged high salt intake.

The influence of prolonged high salt intake on intravascular volume, right atrial pressure, plasma atrial natriuretic factor, and extra-atrial tissue (lung, kidney, and liver) COOH- and NH2-terminal atrial natriuretic factor content was investigated in normotensive rats. Despite prolonged high salt (8% NaCl) intake for 5 weeks, total intravascular volume was not impaired. However, right atrial pressure was increased by 54% (p less than 0.01) after salt loading. Although this increment in right atrial pressure should favor atrial natriuretic factor release after NaCl intake, plasma atrial natriuretic factor (COOH-terminal) concentrations markedly decreased from 97.8 +/- 27 to 38.9 +/- 8 pg/mL. Sodium and circulatory homeostasis was, however, well preserved. The lungs contained the highest levels of COOH- and NH2-terminal atrial natriuretic factor. Salt loading resulted in increased concentrations of low as well as high molecular weight atrial natriuretic factor in the lung but not in the kidney or the liver. Our study indicates a limited role of atrial natriuretic factor in adaptation to prolonged salt consumption in rats. Dissociation between right atrial pressure and plasma atrial natriuretic factor after salt intake implicates other factors regulating circulating peptide levels. Prolonged salt intake increases lung generation of atrial natriuretic factor.

Animals↗
PubMed1990

Regulation of ANG II and AVP receptors in isolated hepatocytes of pregnant rats.

Recent evidence suggests that angiotensin II (ANG II) and vasopressin (AVP) act on the liver via specific receptors. We have examined the binding properties of these receptors in isolated rat hepatocytes and studied the regulation of the biological responses to ANG II and AVP during pregnancy in the rat. In contrast to [3H]ANG II, 125I-labeled-[Sar1-Ile8]ANG II was markedly resistant to degradation by isolated liver cells. Displacement and saturation experiments with this iodinated antagonist revealed the presence of a single class of binding sites [2 x 10(5) sites/cell, dissociation constant (KD) = 1.0 nM]. The potency of ANG II analogues to displace 125I-[Sar1-Ile8]-ANG II agrees closely with data reported for vascular smooth muscle cells. Isolated hepatocytes have approximately 8 x 10(4) [3H]AVP binding sites/cell (KD = 1.0 nM) based on saturation experiments. AVP analogues selectively displaced [3H]AVP, suggesting the presence of V1-AVP receptor subtype. The maximum response of [Sar1]ANG II-induced glycogenolysis in the cells was decreased during gestation, whereas the effective concentration producing 50% of maximum response (EC50) was significantly increased (0.15-0.28 nM) when compared with cells from nonpregnant animals. In pregnancy, receptors for 125I-[Sar1-Ile8]ANG II were not changed in affinity (KD) or in density (Bmax). The maximum response and EC50 of AVP on liver glycogenolysis were not significantly decreased during pregnancy, whereas an increased number of AVP binding sites (from 5.0 +/- 0.5 x 10(4) to 11.0 +/- 1.7 x 10(4)) with similar KD was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗