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Biomedical subjects

G Thibault

Publications and source records attributed to G Thibault.

At least 91 records · Page 5Linked to original sources
PubMed1993

Prognostic significance of N-terminal pro-atrial natriuretic factor (1-98) in acute myocardial infarction: comparison with atrial natriuretic factor (99-126) and clinical evaluation.

OBJECTIVE: To evaluate the prognostic significance of plasma N-terminal pro-atrial natriuretic factor (1-98) concentrations measured in the subacute phase after acute myocardial infarction, and to compare the predictive value of measurement of N-terminal pro-atrial natriuretic factor (1-98) with the measurement of atrial natriuretic factor (99-126) and with clinical assessment of the degree of heart failure. DESIGN: Prospective observational. SETTING: Norwegian central hospital. PATIENTS: 139 patients (mean (SD) age 66.9 (11.1) years, 71.2% males) with acute myocardial infarction. Patients in cardiogenic shock or with severe heart failure (New York Heart Association class IV) were excluded. MAIN OUTCOME MEASURE: Cardiovascular death within 12 months. RESULTS: During the follow up period 15 patients died. In a univariate Cox proportional hazards model N-terminal pro-atrial natriuretic factor (1-98) was significantly related to mortality (p = 0.0003). In a multivariate model the prognostic value of N-terminal pro-atrial natriuretic factor (1-98) was better than that of atrial natriuretic factor (99-126) and clinical assessment of heart failure (N-terminal pro-atrial natriuretic factor (1-98), p = 0.0003; atrial natriuretic factor (99-126), p = 0.4513; heart failure, p = 0.0719). The odds ratio estimate of patients in whom plasma concentrations of N-terminal pro-atrial natriuretic factor (1-98) were greater than 2000 pmol/l was 25 (95% confidence interval 2.8-225.0) compared with patients with plasma concentrations less than 1000 pmol/l. CONCLUSIONS: These results suggest that determination of plasma N-terminal pro-atrial natriuretic factor (1-98) in the subacute phase of myocardial infarction may provide clinically relevant prognostic information that is superior to that obtained from atrial natriuretic factor (99-126) measurements and clinical evaluation.

Aged↗
PubMed1993

Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate-salt hypertensive but not in spontaneously hypertensive rats.

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced in the endothelium of blood vessels that may play an important role in the control of local blood flow and could be involved in the pathogenesis of hypertension. We investigated immunoreactive ET-1 (ir-ET-1) levels in acid extracts from blood vessels of deoxycorticosterone acetate (DOCA)-salt and spontaneously hypertensive rats. We found that segments of thoracic aorta and the mesenteric vascular bed contain significantly more ir-ET-1 (11.84 +/- 0.84 and 17.30 +/- 1.89 fmol, respectively) than uninephrectomized control rats (1.78 +/- 0.20 and 9.19 +/- 0.63 fmol, respectively; p < 0.001). High performance liquid chromatography showed that ir-ET-1 of blood vessels of DOCA-salt hypertensive rats eluted in the same position as synthetic ET-1. Significantly increased ir-ET-1 was localized by immunohistochemistry in endothelial cells of aorta and large and small mesenteric arteries of DOCA-salt hypertensive rats. In contrast to the latter, in spontaneously hypertensive rats, vascular content of ir-ET-1 was similar to that of blood vessels of Wistar-Kyoto control rats, at both 6 and 16 weeks of age. High levels of vascular ET-1 may explain the downregulation of vascular endothelin receptors previously described in DOCA-salt hypertensive rats. Furthermore, this suggests that ET-1 may be involved in the maintenance of high blood pressure in mineralocorticoid hypertension.

Animals↗
PubMed1993

Effect of hypertension induced by nitric oxide synthase inhibition on structure and function of resistance arteries in the rat.

To determine whether inhibition of generation of endothelium-derived relaxing factor or nitric oxide (NO) resulted in elevated blood pressure and its effect on resistance arteries, rats were offered NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, in their drinking water. Blood pressure (BP) rose slightly from 100 +/- 2 mmHg in controls to 130 +/- 5 mmHg with 25 mg/Kg L-NAME per day and to 173 +/- 9 mmHg with 100 mg/Kg per day for 2 1/2 to 4 weeks. Rats were studied after 1-2 weeks of hypertension (BP > 150 mmHg). The concentration of cyclic guanosine monophosphate, the intracellular second messenger of NO, was significantly depressed in aorta and in the mesenteric vascular bed in L-NAME-treated rats. Mesenteric resistance arteries studied on a wire-myograph exhibited similar external and lumen diameters, whereas media width and media/lumen ratio were greater (p < 0.01). Cross-sectional area of the media was similar. Active wall tension in response to norepinephrine tended to be greater in blood vessels from L-NAME-treated rats, while responses to vasopressin and endothelin-1 were unaltered. Sensitivity to norepinephrine was significantly enhanced in L-NAME-treated rats (p < 0.001), while that to endothelin-1 and arginine8 vasopressin was similar. In conclusion, administration of an NO synthase inhibitor produces hypertension, with exaggerated media/lumen ratio in resistance arteries and enhancement of response to norepinephrine, which together with decreased NO generation may contribute to elevation of blood pressure.

Amino Acid Oxidoreductases↗
PubMed1992

Autoradiographic visualization of the natriuretic peptide receptor-B in rat tissues.

Natriuretic peptide receptor-B (NPRB) was visualized in rat tissues by in vitro autoradiography, using its putative physiological agonist C-type natriuretic peptide (CNP). In initial studies, we determined that atrial natriuretic peptide (ANP) is not a suitable ligand for labeling the NPRB: in tissues reported to contain NPRB transcripts, CNP did not inhibit [125I]ANP binding except to NPRC sites. Therefore, to visualize the NPRB we used 125I[Tyr(o)]-CNP as a radioligand with an excess of NPRC-blocking peptide: C-ANP. With this approach we detected the highest number of NPRB-like sites in the pars intermedia of the pituitary gland. A large number of these sites were present in pituitary neural and anterior lobes, area postrema, adrenal medulla and cortex. A moderate NPRB population was observed in the subfornical organ, plexiform layer of the olfactory bulb and kidney. Low concentrations of NPRB were noted in the cerebellum and cerebrum but not in the choroid plexus and pia-arachnoid. Saturation experiments performed on cerebellum sections revealed a very low concentration (Bmax 4.8 fmol/mg protein) of high affinity (Kd 1.2 nM) NPRB-like sites. This study is the first demonstration of 125I[Tyr(o)]-CNP binding sites with characteristics of the NPRB in intact tissues.

Adrenal Glands↗
PubMed1992

Decreased plasma atriopeptin response to volume-overloading maneuvers and exercise after atriopulmonary anastomosis of Fontan.

Atriopulmonary anastomosis results in a chronic right atrial pressure-volume overload. Water and salt retention is a frequent clinical observation in patients after atriopulmonary anastomosis. The purpose of this study was to examine if this could be related to an inability to increase already elevated circulating atriopeptin (ANP) in response to central volume-overloading conditions. Eighteen patients (mean age 16 +/- 6 years) with an atriopulmonary anastomosis underwent routine cardiac catheterization during which a 5-minute head-down 10 degrees tilt was performed. Peripheral venous and right atrial blood samples were obtained under basal conditions, and after tilting and angiography for determination of ANP concentrations. At a different time, circulating ANP levels were measured during a maximal graded exercise protocol. Increased circulating ANP concentrations were found under basal conditions (114 +/- 10 pg/ml). Tilting and cardioangiography resulted in significant increases in mean atrial pressure (basal: 12 +/- 0.7 mm Hg; tilt: 13.4 +/- 0.63 mm Hg; after angiography: 15.8 +/- 0.8 mm Hg), but not in atrial or peripheral ANP. Compared with the expected threefold increase in plasma ANP induced by maximal exercise in healthy control subjects, only a slight (0.25-fold) increase was found in patients. These observations suggest a reduced stimulus-release response after atriopulmonary anastomosis, which could be related to a loss of atrial stretch receptor sensitivity, achievement of the limit for maximal right atrial secretion, or an alteration in right atrial compliance, or a combination.

Adolescent↗
PubMed1992

Role of the liver in splanchnic extraction of atrial natriuretic factor in the rat.

Mesenteric, hepatic and splanchnic extraction of C-terminal and N-terminal atrial natriuretic factor was investigated in male Sprague-Dawley rats. Plasma concentrations (mean +/- S.E.M.) of C-terminal atrial natriuretic factor were 55.0 +/- 6.1 fmol/ml, 31.2 +/- 4.0 fmol/ml and 23.5 +/- 3.3 fmol/ml (n = 12) in the abdominal aorta, the portal vein and the hepatic vein, respectively. N-terminal atrial natriuretic factor plasma levels in these vessels were 3031 +/- 756 fmol/ml, 2264 +/- 661 fmol/ml and 1618 +/- 496 fmol/ml (n = 6), respectively. Although the mesenteric extraction ratio was higher (p less than 0.05) for C-terminal atrial natriuretic factor (42% +/- 6%) than for N-terminal atrial natriuretic factor (28% +/- 4%), there were no significant differences in the hepatic extraction ratio (41% +/- 5% vs. 39% +/- 6%) and the splanchnic extraction ratio (56% +/- 5% vs. 50% +/- 7%). These data suggest a major role of the liver in the splanchnic extraction of C-terminal and of N-terminal atrial natriuretic factor in the rat.

Animals↗
PubMed1992

Inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on Jurkat cells activated by phorbol ester and calcium ionophore.

The effects of syncytiotrophoblast plasma membrane vesicles (STPM) on stimulated Jurkat leukemic T cells have been investigated. STPM inhibited IL-2 production and the expression of protein P55 of the IL-2 receptor (IL-2R P55), when Jurkat cells were stimulated by a combination of calcium ionophore A23187 (CaI) + phorbol 12-myristate 13-acetate (PMA). STPM also inhibited IL-2R P55 when cells were stimulated by PMA alone, a situation in which IL-2 production is negligible. On the other hand, STPM had no effect on the sustained mobilization of intracellular Ca2+ induced by CaI nor on the PKC-dependent CD3 down regulation induced by PMA. Finally STPM had no effect on intracellular cAMP levels. These results show that (i) the inhibitory effect of STPM on IL-2R P55 expression is independent of the inhibition of IL-2 production, and (ii) the inhibitory effects of STPM are at least partially independent of phosphatidylinositol 4,5-bisphosphate hydrolysis. They suggest that STPM affect a signaling pathway activated by PMA but possibly PKC independent.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Lipid and protein components of the syncytiotrophoblast plasma membrane inhibit lymphocyte proliferation by two distinct pathways.

The ability of syncytiotrophoblast plasma membrane lipid and protein fractions (STPM lipids, STPM proteins), tested under a reconstituted form, to inhibit lymphocyte proliferation induced by PHA was investigated. The cytostatic activity of STPM proteins appeared greater than that of the STPM lipids. Furthermore, IL-2 production and IL-2 receptor expression by activated lymphocytes were markedly decreased in the presence of STPM proteins compared to the native membrane but remained unaffected in the presence of STPM lipids. Finally, the inhibition of lymphoproliferation could be maintained after removal of the protein fraction from lymphocytes prior to stimulation by PHA. The biological and immunological significance of these results is discussed.

Cell Division↗
PubMed1992

Vascular atrial natriuretic factor receptors in spontaneously hypertensive rats.

OBJECTIVE: The aim was to investigate vascular receptors for atrial natriuretic factor (ANF) in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats (WR) at different ages. METHODS: Relaxation and guanylate cyclase responses of blood vessels to atrial natriuretic factor were investigated, as was the binding of 125I-ANF to vascular membranes and ANF receptor subtypes, using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in reducing conditions, after solubilisation and irreversible binding of 125I-ANF. RESULTS: Vascular relaxation responses of aorta showed an increased sensitivity to ANF in four week old SHR [pD2 = 8.9 (SEM 0.1) v 8.5(0.1) in WKY rats, p < 0.05] while sensitivity was similar for the three strains at older ages. Production of cyclic GMP in mesenteric arteries in response to 100 nmol.litre-1 ANF was greater (p < 0.05) in SHR than in WKY rats at four weeks of age, but was similar in older rats. The density of binding sites for ANF in mesenteric arteries, however, was lower in SHR at four weeks (p < 0.01), and increased in older rats, becoming similar to that of normotensive rats at 12 weeks of age. Affinity of ANF sites was similar in all strains. The proportion of high and low molecular weight ANF binding peptides in solubilised blood vessel membranes on SDS-PAGE was similar in all strains except in four week old SHR, in which binding to the high molecular weight band (presumably the guanylate cyclase containing receptor) was increased relative to the low molecular weight band (non-cyclase-coupled receptor) in comparison to other strains and ages. CONCLUSIONS: Activity of guanylate cyclase in response to occupancy of ANF receptors may be increased in young SHR. Normal relaxation of blood vessels in response to ANF in older SHR could result in failure to counteract the increased vasoconstrictor activity present in these rats, which could play a role in the increase in blood pressure.

Animals↗
PubMed1992

Interleukin 4 and tumour necrosis factor alpha induce different adhesion pathways in endothelial cells for the binding of peripheral blood lymphocytes.

We demonstrated that tumour necrosis factor alpha (TNF-alpha) and interleukin 4 (IL-4) increased endothelial cell (EC) adhesiveness for peripheral blood lymphocytes (PBL) by promoting transcription and protein synthesis. The different kinetics observed with TNF-alpha and IL-4 suggest the involvement of different adhesion molecules. Blocking adhesion assays and immunofluorescence analysis showed that PBL adhesion to endothelial cells involves different pair adhesion molecules. Whereas IL-4 promoted an LFA-1-dependent/ICAM-1-independent adhesion pathway on EC, TNF-alpha stimulated an LFA-1-dependent/ICAM-1-dependent adhesion pathway on EC. In contrast, VLA-4/VCAM-1 molecules were involved in PBL adhesion both to IL-4 and to TNF-alpha-stimulated EC. Finally, we found that a CD2-dependent/LFA-3-independent adhesion pathway was mainly involved in IL-4-stimulated EC.

Antigens, CD↗
PubMed1992

Binding and aggregation of pro-atrial natriuretic factor by calcium.

Analysis of atrial secretory granule content by sodium dodecyl sulfate-gel electrophoresis followed by a 45Ca2+ overlay assay indicates that a 17,000 protein binds 45Ca2+. This protein, which can be immunostained by atrial natriuretic factor (ANF) antiserum, corresponds to proANF. Ca2+ binding is proportional to the amount of proANF and pH dependent. Generation of ANF-(1-98) by thrombin digestion of proANF does not affect Ca2+ binding. Blocking the carboxyl groups of proANF and the use of NH2-terminal fragments bearing those carboxyl groups demonstrated that the Ca(2+)-interaction site is probably located within the highly acidic portion (11-30) of the propeptide. Ca2+ binding to proANF induces its aggregation that can be verified by sedimentation. ProANF aggregation is Ca2+ dependent, being optimal at 10 mM, partially pH dependent, and greatly increased by high concentrations of proANF. However, because of its relatively low-binding affinity, Ca2+ can be substituted by other divalent cations such as Sr2+, Ba2+, or Mg2+. The high level of Ca2+ in atrial secretory granules and the aggregation of proANF in the presence of Ca2+ suggest a possible involvement of these physicochemical properties in the condensed state of the matrix of secretory granules. Indeed, detergent solubilization of the membrane of the secretory granules in presence of Ca2+ resulted only in a partial dissolution of the dense core matrix. We therefore postulate that, in the Golgi complex, proANF and Ca2+ associate to form a condensed aggregate that helps package secretory material into secretory vesicles.

Animals↗
PubMed1992

Rat brain natriuretic peptide is localized in atrial granules and released into the circulation.

Rat brain natriuretic peptide (BNP) was detected by radioimmunoassay in heart atria and ventricles and in plasma. We have investigated its localization in atria and the possibility of cosecretion of atrial natriuretic factor (ANF) and BNP into the circulation. BNP was detected by chromatographic analysis and immunoblotting in the isolated atrial granules together with ANF: It consisted of two immunoreactive proteins of 14,000 and 2,500 apparent molecular weight. By immunohistochemical methods, BNP was particularly found in the perinuclear region of atrial cardiocytes. Double-labeling immunocytochemical methods colocalized BNP and ANF in the same atrial secretory granules. Basal plasma BNP levels ranged from 2.6 to 4.4 fmol/ml. After stimuli by morphine injection or an aortocaval shunt, BNP levels increased by 4- and 7-fold, respectively, whereas ANF levels rose by 50- and 6-fold, respectively. Depending on the stimulus, BNP release into the circulation is not necessarily proportional to ANF, indicating that BNP may originate not only from the atrial granules but also from other tissues such as the ventricles. These results suggest that BNP may participate with ANF in blood pressure control and salt and water homeostasis.

Animals↗
PubMed1992

Atrial natriuretic factor binding sites in rat area postrema: autoradiographic study.

The area postrema (AP) is a brain stem circumventricular organ implicated, among other functions, in central cardiovascular (CV) regulation. Competition binding analysis performed by quantitative in vitro autoradiography demonstrated specific, high-affinity (Kd, 0.32 +/- 0.11 nM), low-capacity (Bmax, 57.5 +/- 10.9 fmol/mg protein) atrial natriuretic factor (ANF) binding sites in the AP. C-ANF [des-(Gln116-Gly120)ANF-(Arg102-Cys121)-NH2] and ANF-(Phe106-Ile113)-NH2 (two ligands endowed with selectivity for the ANF-C receptor), as well as C-type natriuretic peptide (CNP), did not compete noticeably at pathophysiological concentrations for 125I-ANF binding. 125I-[Tyr0]CNP bound to the AP to a much lower extent than 125I-ANF. Electron microscopic autoradiography in vivo disclosed that 125I-ANF was preferentially bound to axon, dendrite, and astrocyte plasmalemma. These studies demonstrate that the AP contains natriuretic peptide binding sites with pharmacological characteristics of the ANF-A and ANF-B but not of the ANF-C receptor subtype. In the AP, ANF interacts with those sites resembling ANF-A receptors. Cellular localization of these binding sites may relate to their possible involvement in the centrally mediated salt and water regulation and/or CV effects of circulating ANF.

Animals↗
PubMed1992

Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats.

The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2 +/- 0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA-salt rats (106 +/- 22 fmol/mg protein) than in uninephrectomized rats (172 +/- 19 fmol/mg protein, p less than 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with [3H]myoinositol. Inositol phosphates were separated by high-performance liquid chromatography. In response to 100 nmol/l ET-1, accumulation of inositol 1,4,5-trisphosphate after 20 seconds and of inositol monophosphate, inositol bisphosphate, and inositol 1,3,4-triphosphate after 30 minutes (in the presence of 25 mmol/l LiCl) were significantly lower in DOCA-salt hypertensive than in uninephrectomized control rats, in both aorta and mesenteric arteries. In conclusion, decreased density of ET-1 receptors in DOCA-salt hypertensive rats results in decreased activation of phospholipase C and, consequently, reduced vasoconstriction induced by ET-1. Because the decrease in vasoconstrictor effects of ET-1 is found in the absence of endothelium, it is likely that receptor downregulation rather than prior receptor occupancy underlies these findings.

Animals↗
PubMed1992

Effect of ketoprofen on blood pressure, endocrine and renal responses to chronic dosing with captopril in patients with essential hypertension.

The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered. Twelve patients with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or matching placebo in a randomized double-blind cross-over fashion. A 3-week wash-out period was included between treatment periods. Blood pressure on the first and last days of the placebo treatment period (137 +/- 7 (SD)/80 +/- 8 and 139 +/- 11/81 +/- 9 mmHg) was similar to respective values during ketoprofen therapy (136 +/- 10/79 +/- 7 and 143 +/- 10/81 +/- 9 mmHg). The mean differences in systolic and diastolic blood pressures, at the end of the treatment periods, between ketoprofen and placebo were 4 (95% confidence intervals -5, +13) and 0 (-8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium excretion (160 +/- 33 and 147 +/- 39 mmol/24 h for ketoprofen and placebo, respectively). Ketoprofen was without effect on glomerular filtration rate, renal plasma flow and filtration fraction. In conclusion, our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril.

Adult↗
PubMed1991

Region-specific immunolocalization of atrial natriuretic peptide in mixed fetal rat brain cell cultures.

In adult rodent CNS, atrial natriuretic peptide (ANP) has been localized by immunolabeling and nucleic acid hybridization techniques primarily to hypothalamic neurons and, to a lesser extent, to neurons of the telencephalon and brainstem. In canine brain, ANP immunoreactivity has been reported in neocortical and brainstem astrocytes. Yet, in a recent study using fetal rat tissue, ANP was detected by radioimmunoassay in predominantly neuronal, but not glial, cultures. In the present study ANP was detected by radioimmunoassay on in vitro day 8 in media derived from fetal rat diencephalic and rhombencephalic, but not telencephalic, cultures and in cell homogenates from all 3 regions surveyed. Using indirect immunofluorescence less than one cell per 400x field stained for ANP in the telencephalic cultures and ANP immunopositivity colocalized exclusively to neurons by concomitant anti-neurofilament immunolabeling. In diencephalic monolayers, approximately 1-3 cells per 400x field were ANP-positive; although most of these cells were neurons, small numbers of ANP-positive astrocytes were also detected using anti-glial fibrillary acidic protein (GFAP) immunolabeling. ANP-positive cells were most numerous in rhombencephalic cultures (5-10 cells per 400x field); as in diencephalic cultures, ANP immunoreactivity colocalized to both neurons and astrocytes in this region. In diencephalon and rhombencephalon, less than 1% of all ANP-positive cells were astrocytes and less than 1% of GFAP-positive astrocytes exhibited immunoreactive ANP. In fetal brain, neuronal and astrocytic ANP may play a role in fluid and electrolyte homeostasis. Alternatively, fetal brain cell ANP may subserve entirely different functions (e.g. as trophic factors) as has been suggested for other neuropeptides in the developing nervous system.

Animals↗