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A Bataillard

Publications and source records attributed to A Bataillard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Soman-induced hypertension in conscious rats is mediated by prolonged central muscarinic stimulation.

The acetylcholinesterase inhibitor, soman, induces marked and sustained hypertension and tachycardia associated with a convulsive syndrome in rats. The aims of the present study were to distinguish between the cardiovascular and convulsant effects of soman and to determine whether the maintenance of the soman-induced hypertension and tachycardia depends solely on a central muscarinic effect. To this end, using a computerised analysis of blood pressure (BP) in conscious freely moving rats, we examined the consequences on the increase in mean BP (MBP) and heart rate (HR) induced by soman (60 micrograms/kg, i.v.) of 1) a pre-treatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.) and 2) atropine sulphate (10 mg/kg, i.v.) administered 10 or 60 min after the intoxication. Pretreatment with diazepam prevented the convulsions, assessed by electroencephalogram (EEG) recording, but modified neither the magnitude nor the kinetics of the pressor and tachycardic effects of soman (delta MBP = 74 +/- 2 and 73 +/- 5 mmHg, delta HR = 69 +/- 10 and 79 +/- 7 bpm, maximum MBP = 186 +/- 3 and 182 +/- 6 mmHg, maximum HR = 545 +/- 9 and 522 +/- 16 bpm in solvent- (n = 8) and diazepam- (n = 8) pre-treated rats, respectively). Whatever its time of administration, atropine sulphate fully and immediately reversed the rise in BP induced by soman. The soman-induced tachycardia was also suppressed by atropine administered 10 min after soman whereas it persisted when atropine was injected 60 min after the intoxication. These results show that the cardiovascular effects of soman can occur independently of the convulsive syndrome and that the maintenance of the soman-induced hypertension depends entirely on a permanent central muscarinic stimulation.

Animals↗
PubMed1999

Pharmacological properties of indapamide. Rationale for use in hypertension.

Indapamide is a thiazide-related diuretic drug with antihypertensive properties. Its blood pressure-lowering action has been repeatedly demonstrated in acute as well as chronic conditions in various genetically and nongenetically determined forms of hypertension. In rats, the maximally effective oral dose is 3 mg/kg/24 h. The natriuretic effect of indapamide peaked at 3-fold at a dose of 1 mg/kg. In accordance with its antihypertensive properties, indapamide was shown to have excellent efficacy in protecting against target organ damage (heart, kidneys, brain). In addition to its natriuretic effect, it has been shown in several experiments that indapamide lowers the response to sympathetic nerve stimulation, exhibits calcium antagonist properties, enhances the production of prostacyclin, and limits the production of free radicals and of endothelium-dependent vasoconstrictor substances. These effects, even though they are observed at high indapamide concentrations and in a possibly species-dependent manner, may contribute to the beneficial properties of indapamide. The most recent data suggest that low doses of indapamide exert synergistic effects in combination with other antihypertensive drugs such as ACE inhibitors, the effects of which are influenced by the sodium status of the organism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Lack of insulin resistance in the Lyon hypertensive rat.

Genetically hypertensive rats (LH) of the Lyon strain, compared to their normo-tensive (LN) controls associate, in a unique manner, high blood pressure with increases in body weight and in plasma lipids and insulin/glucose ratio. The present work investigated the development of insulin resistance with age in this model. At the age of 22 and 52 weeks, LH and LN fasted male rats were submitted to an intravenous glucose tolerance test, allowing measurement of the elimination rate of the glucose and the area under the curve of the insulin response. Insulin sensitivity was calculated as the ratio of these two parameters. It was observed that insulin sensitivity coefficient decreased with age in all the animals and that LH rats did not significantly differ from LN controls (from 62.6 +/- 3.3 and 69.1 +/- 4 at 22 weeks to 42.1 +/- 4.4 and 49.5 +/- 12.8 at 52 weeks for LH and LN rats, respectively). It is concluded that 1) elevated plasma insulin/glucose ratio does not mean insulin resistance and 2) hypertension can develop without being associated, even in aged rats, to a true insulin resistance.

Age Factors↗
PubMed1996

Antihypertensive effect of thymectomy in Lyon hypertensive rats. Vascular reactivity, renal histology, and sodium excretion.

The aim of this study was to search for the possible mechanisms involved in the antihypertensive effect of neonatal thymectomy that we previously observed in Lyon hypertensive (LH) rats. To that end, we studied in LH and normotensive control (LN) rats the consequences of neonatal thymectomy on vascular reactivity, renal structure, and pressure-natriuresis. The increase in pressor responses to angiotensin I and phenylephrine noted in LH rats as compared to LN animals was abolished by neonatal thymectomy. Histological study showed that kidneys from LH rats exhibited arterial wall hypertrophy, segmental hyalinization of the glomeruli, and were infiltrated by mononuclear cells. All these features of kidney injury were reduced in neonatally thymectomized LH rats. Lastly, the responses of isolated perfused kidneys from LH rats to stepwise reductions in renal perfusion pressure differed from those of LN rats by decreased renal perfusion flow and natriuresis. Neonatal thymectomy tended to improve sodium excretion in parallel with a slight decrease in renal vascular resistances. It is concluded that the normalization of vascular responsiveness to vasoconstrictor factors, the alleviation of renal lesions and, to a lesser extent, the moderate improvement of pressure natriuresis may account, at least in part, for the antihypertensive effect of neonatal thymectomy in LH rats.

Animals↗
PubMed1995

Silica attenuates hypertension in Lyon hypertensive rats.

BACKGROUND AND OBJECTIVE: Evidence has been provided suggesting an association between hypertension and immune dysfunction in Lyon hypertensive (LH) rats. In the present study, we investigated the possible role played by macrophages in LH rats by examining the blood pressure consequences of the chronic administration of silica, a selective toxin to macrophages in vivo. DESIGN AND METHODS: LH and Lyon low blood pressure (LL) male rats were treated with silica at a dose of 200 mg/kg per week intraperitoneally from age 4-10 weeks. Controls received saline. Blood pressure was measured by plethysmography from age 6-10 weeks and an intra-arterial recording was performed in 11-week-old, freely moving rats. RESULTS: Treatment with silica did not modify blood pressure in LL rats at any age. In contrast, 1 week after the beginning of the treatment, the blood pressure of silica-treated LH rats was lower than that of untreated LH rats. As shown by intra-arterial recording, the effect persisted 1 week after cessation of the treatment. In addition, silica decreased the left ventricle weight in LH but not in LL rats. CONCLUSION: The present results show that weekly administration of silica in young LH rats attenuates the development of hypertension and of left ventricular hypertrophy, a finding which suggests that macrophage-mediated immune reactions may play a pathogenic role in LH rats.

Animals↗
PubMed1995

Partial transfer of genetic hypertension by lymphoid cells in Lyon rats.

BACKGROUND AND OBJECTIVE: The involvement of immune factors in a given disease is suggested by evidence that a disease can be prevented by immunosuppression and can be transferred by lymphoid cells. Because the first type of experimental result was achieved in Lyon hypertensive (LH) rats, the present study was undertaken to determine whether hypertension can be transferred to normotensive recipients. As a control, the blood pressure effects of lymphoid cell grafts from renovascular hypertensive donors were also determined. DESIGN AND METHODS: Splenocytes and lymph node cells from LH and Lyon low-blood pressure (LL) rats with two-kidney Goldblatt hypertension were respectively injected into LH x Lyon normotensive (LN) F1 hybrids and LL rats aged 7, 8, 9 and 10 weeks. Blood pressure was measured by plethysmography from age 6 to 13 weeks and an intra-arterial recording was performed in 14-week-old conscious rats. RESULTS: Lymphoid cell injections from LL rat donors with two-kidney hypertension did not modify the blood pressure of LL rat recipients. In contrast, lymphoid cell grafts from LH rat donors induced a significant increase in blood pressure in F1 recipients compared with control F1 rats after the first injection. As confirmed by intra-arterial recording, this blood pressure effect lasted until age 14 weeks (145 +/- 1 versus 137 +/- 1 mmHg in grafted and ungrafted F1, respectively). It was not related to alterations in the acute role of the renin-angiotensin and sympathetic nervous systems and was not associated with increased pressor responses to the vasoconstrictor drugs tested. CONCLUSION: The present study demonstrates that genetic hypertension can be partially transferred by lymphoid cells in F1 recipients. The effect seems to be specific to genetic hypertension because lymphoid cells from renovascular hypertensive donors failed to transfer this secondary form of hypertension. The present results support the hypothesis that cellular immune reactions contribute to the pathogenesis of hypertension and LH rats.

Animals↗
PubMed1994

Cardiovascular effects of human recombinant interleukin-1 beta in conscious rats.

Cardiovascular effects of human recombinant interleukin-1 beta (hrIL-1 beta) were investigated in normotensive rats using a computerized analysis of arterial blood pressure in conscious, unrestrained animals. Intravenous injection of hrIL-1 beta induced a rapid and short-lasting rise in blood pressure associated with a first slight tachycardia followed by a second sustained and pronounced increase in heart rate. These effects occurred in a dose-related manner. Pretreatment with a converting-enzyme inhibitor (perindopril) did not modify the hrIL-1 beta-induced increase in blood pressure. Blockade of beta 1-adrenoceptors (atenolol) prevented the tachycardia, but did not significantly affect the pressor response to hrIL-1 beta. On the contrary, the hrIL-1 beta-induced increase in blood pressure was inhibited by an alpha 1-adrenoceptor antagonist (prazosin), whereas the tachycardia was untouched. Finally, pretreatment with a cyclooxygenase inhibitor (indomethacin) completely abolished the cardiovascular response to hrIL-1 beta. These results suggest that the hrIL-1 beta-induced pressor response and associated tachycardia require the synthesis of prostaglandins and involve a sympathetic nervous system activation but do not depend on the renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Do thymic-neuroendocrine interactions play a role in the antihypertensive effect of neonatal thymectomy in Lyon hypertensive rats?

Previous studies showed that neonatal thymectomy prevented the spontaneous increase in blood pressure in genetically hypertensive rats (LH) of the Lyon strain, leaving untouched that of their normotensive controls (LN). As the thymus is connected to the neuroendocrine system through secretion of hormonal factors, we investigated the possible role played by these factors in hypertension of LH rats. To that end we studied, in sham-operated and neonatally thymectomized LH rats, the blood pressure effects of thymostimulin, a partially purified thymus extract and examined whether changes in major neuroendocrine factors of blood pressure regulation occurred in thymectomized LH rats. Thymostimulin (1 or 10 mg/kg/48 h) did not modify blood pressure in sham-operated LH rats and failed to consistently increase it in neonatally thymectomized animals. Urinary mineralocorticoids, catecholamines and their metabolites, and plasma renin levels were not altered by neonatal thymectomy. Plasma testosterone was decreased to a similar degree by neonatal thymectomy in LH and normotensive controls. These results do not favor a pressor role of thymic hormonal factors in LH rats and show that the antihypertensive effect of neonatal thymectomy is not secondary to a decreased secretion of catecholamines, renin, mineralocorticoids, and testosterone. They therefore suggest that the role of the thymus in genetically hypertensive LH rats is more likely mediated by cellular immune mechanisms than by hormonal processes.

Animals↗
PubMed1992

Interleukin-1 stimulates aldosterone secretion: involvement of renin, ACTH, and prostaglandins.

Interleukin-1 (IL-1), a cytokine produced during infection and inflammation, mediates some of the endocrinological alterations that parallel these processes. The purpose of this study was to determine whether human recombinant IL-1 (hrIL-1) affects aldosterone output as well as renin and adrenocorticotropic hormone (ACTH) release, two key factors in the regulation of mineralocorticoid secretion. We observed that intravenous administration of hrIL-1 into conscious unrestrained rats elicited a marked and rapid rise in aldosterone plasma levels in a dose-dependent manner. The hrIL-1-induced increase in aldosterone levels was associated with enhanced renin activity and increased ACTH levels in plasma. Furthermore, aldosterone levels of IL-1-injected rats were positively correlated with plasma renin activity (PRA), suggesting that the renin-angiotensin system contributes to the changes observed in the levels of the mineralocorticoid hormone. ACTH seems also to be implicated in the aldosterone response to hrIL-1 because the profile of the kinetic curves of changes in the levels of the pituitary hormone and aldosterone was similar. Pretreatment with the cyclooxygenase inhibitor indomethacin markedly reduced the increase in aldosterone plasma levels and PRA induced by IL-1, indicating that prostaglandins are involved in these effects of the cytokine. These results suggest that IL-1 may play an important role in the control of homeostasis during infectious and inflammatory diseases.

Adrenocorticotropic Hormone↗
PubMed1991

Fetal liver cell transplantation fails to transfer hypertension from genetically hypertensive rats to normotensive rats of the Lyon strain.

The involvement of an auto-immune mechanism has been suggested in the development and/or the maintenance of hypertension in male, genetically hypertensive rats of the Lyon strain (LH). The aim of this study was to determine whether hypertension may be transferred, by lymphoid cells, from hypertensive donors to male, normotensive rats of the Lyon strain (LN). Experiments designed to induce a resistance to hypertension in LH rats by transfer of lymphoid cells from LN animals were also performed. Since LH and LN are mismatched at the major histocompatibility complex, transfers of fetal liver cells (FLC) from fetuses of 13-14 days gestation were performed. These experiments demonstrate the ability of FLC to allow a prolonged survival (over 17 weeks) without graft versus host disease in the rat. As regards the blood pressure level, no LN recipient having received FLC from LH donor became hypertensive, thus showing that hypertension cannot be transferred by lymphoid cells in normotensive animals. Resistance to hypertension was so weakly transferred to hypertensive rats (results being significantly different only at 10 weeks post-grafting) that it may be considered doubtful.

Animals↗
PubMed1990

Cardiovascular consequences of organophosphorus poisoning and of antidotes in conscious unrestrained rats.

The cardiovascular effects of two organophosphorus, paraoxon and soman, as well as of antidotes advocated in the treatment of these intoxications have been investigated using a computerized analysis of arterial blood pressure in conscious unrestrained rats. Intravenous administration of paraoxon as well as of soman produced a marked, sustained and dose-related increase in blood pressure associated with a bradycardia. Pyridostigmine, a quaternary carbamate, neither altered blood pressure nor heart rate. Benzodiaxepines, such as diazepam or loprazolam, and atropine induced a dose-dependent tachycardia while pralidoxime decreased heart rate. A complete therapeutic scheme including the intravenous administration of pyridostigmine 10 min. before a postpoisoning therapy made of pralidoxime, diazepam and atropine induced a transient tachycardia, which was followed, after a return to control values, by a second and more stable tachycardia concurrently to a slight hypertension. Postpoisoning therapy alone suppressed the pressor effect of soman within a few minutes after its administration. Afterwards, this therapy reduced the importance of the cardiovascular effects produced by soman. Pyridostigmine pretreatment decreased the protection afforded by postpoisoning therapy in soman-intoxicated rats. These results show that postpoisoning therapy with pralidoxime, diazepam and atropine has a noteworthy efficacy against cardiovascular manifestations of soman intoxications in the rat.

Animals↗
PubMed1989

Antihypertensive effect of an immunosuppressive agent, cyclophosphamide, in genetically hypertensive rats of the Lyon strain.

The effect of a pharmacological immunosuppression on the development of hypertension and the part played by hormonal secretions of the thymus in this disease were investigated in genetically hypertensive rats (LH) of the Lyon strain. For this purpose, systolic blood pressure (SBP) was measured in cyclophosphamide-treated LH rats and in neonatally thymectomized LH rats receiving thymostimulin, a thymus extract. Cyclophosphamide treatment delayed the onset and attenuated the full development of hypertension in LH rats whereas it had no effect on SBP in normotensive rats (LN). Thymectomized LH rats also exhibited a significantly decreased SBP as compared to sham-operated controls. Thymostimulin treatment slightly increased the SBP of thymectomized LH rats but did not restore it to the level seen in sham-operated animals. These results showed that thymic hormonal secretions did not seem to be involved in the initiation of hypertension. By contrast, the fact that a reduction of hypertension could be obtained either by thymectomy or cyclophosphamide treatment suggested that immune disorders, mediated by thymus-dependent cellular reactions, could be of pathogenic importance in the development of hypertension in LH rats.

Aging↗
PubMed1989

Steroids during development of genetic hypertension in rats of Lyon strain.

The urinary excretion and the plasma concentration of deoxycorticosterone (DOC), corticosterone, 18-hydroxy-DOC (18-OH-DOC), aldosterone, and 19-nor-DOC were measured by specific radioimmunoassays in genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) male rats of the Lyon strains at two ages that characterize the development of their systolic blood pressure (SBP). When compared with both LN and LL controls, 5-wk-old LH rats exhibited an increased urinary DOC and decreased urinary corticosterone excretions, which were significantly related to the SBP level (r' = 0.618 and -0.520; n = 23; P less than 0.01 for DOC and corticosterone, respectively). In addition, the adrenal synthesis of LH rats was found to rely on an increased 18-hydroxylase activity as indicated by elevated urinary 18-OH-DOC/corticosterone and aldosterone/corticosterone associated with a lower 11-beta-hydroxylase activity shown by the decreased urinary corticosterone/DOC. Twenty-wk-old LH rats with fully developed hypertension exhibited normal urinary excretion of steroids and a decrease in plasma DOC concentration, which negatively correlated with the SBP level (r' = -0.574; n = 25; P less than 0.01). In conclusion, the present study demonstrates that in the Lyon model of genetically hypertensive rats, compared with two genetically different control strains and maintained under physiological unstressed conditions, the development of hypertension is associated with an increased urinary excretion of DOC. After the full development of their hypertension, the mineralocorticoid synthesis in LH rats returns to normal or low levels which could, however, remain inappropriately high for their sodium body content.

Adrenal Cortex Hormones↗
PubMed1988

Mineralocorticoids are not involved in the antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strain. Sham-operated animals served as controls. 2. Neonatal thymectomy prevented the spontaneous increase of SBP in LH rats while it slightly decreased the SBP of LN and did not change that of LL rats. 3. Five week old sham-operated LH rats exhibited an increased urinary excretion of DOC and a decreased excretion of B compared with both LN and LL controls. Thymectomy did not alter the urinary excretion of adrenal steroids in LN and LL rats. The urinary excretion of B was markedly enhanced in thymectomized LH rats whereas that of DOC remained unmodified. 4. These data suggested that the thymus could be involved in the development of hypertension in LH rats. 5. The antihypertensive effect of thymectomy did not seem to be mediated by a decreased mineralocorticoid production in the genetically hypertensive rat of the Lyon strain.

Aldosterone↗
PubMed1986

[Effect of the thymus on the development of genetic hypertension in the Lyons-strain rat (LH)].

The aim of this work was to determine the part played by the thymus in the development genetic hypertension. This study was conducted in the genetically hypertensive rats (LH) of the lyon strain and their two simultaneously selected controls: the normotensive (LN) and low blood pressure (LL) rats. Systolic blood pressure (SBP) and immunological characteristics were investigated in sham-operated and neonatally thymectomized rats of the 3 strains. At 5 weeks of age, sham-operated LH rats exhibited a higher SBP (122 +/- 4 mmHg) than LN (111 +/- 2 mmHg) and LL (100 +/- 2 mmHg) controls. White blood cell numbers and percentage of circulating lymphocytes, thymus histology as well as T cells and T subsets percentages in that organ did not significantly differ within the 3 strains. On the contrary, in the animals of the 3 strains, a positive relationship could be established between the SBP and the proliferative response of the splenocytes to Pokeweed-Mitogen (r = 0.93; N = 30; p less than 0.001) or to Concanavalin A (r = 0.42; n = 30; p less than 0.05). After neonatal thymectomy the SBP of LH rats was more markedly decrease than that of LN and LL rats and established as follows: 103 +/- 2 mmHg; 102 +/- 2 mmHg; 97 +/- 2 mmHg for LH, LN and LL respectively. 21 weeks after thymectomy the SBP remained significantly decrease in LH rats only 160 +/- 5 mmHg vs 177 +/- 6 mmHg in sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

Genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strains have been simultaneously selected according to their systolic blood pressure (SBP). SBP and immunological parameters were investigated in 5 week-old rats. SBP reached 99 +/- 2 mmHg in LL, 108 +/- 2 mmHg in LN and 122 +/- 4 mmHg in LH. White blood cell and lymphocyte counts, thymus and spleen histology, percentages of T cells and subsets of T cells in these organs were not modified by genetic hypertension. The blastogenic responses to mitogens (Con A and PWM) of the LH rat thymocytes were similar to those observed in LN or LL rats. By contrast, the proliferative response of splenocytes to PWM was positively correlated (r = 0.93) with SBP level. In additional experiments we demonstrated that, besides the immune defect induced by neonatal thymectomy, the removal of the thymus at birth prevented the spontaneous increase of SBP in LH strains (102 +/- 2 mmHg instead of 122 +/- 4 mmHg), while only a slight decrease or no alteration was seen in LN and LL thymectomized rats. This antihypertensive effect tended to maintain SBP at a common level in the 3 strains. These results suggest that the thymus may be involved in the development of genetic hypertension.

Animals↗
PubMedDate not supplied

[Concomitant radiochemotherapy for cancer of the cervix: critical analysis based on the Standards, Options and Recommendations methodology].

INTRODUCTION: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the National Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres (CRLCC) and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To update, according to the methodology of SOR, the Standards, Options and Recommendations for the management of patients with cancer of the cervix, and in particular, the place of concomitant radiochemotherapy. METHODS: Data have been identified by a literature search using Medline (to April 1999) and the personal reference lists of experts. Once the guidelines were defined, the document was submitted for review to independent national and international reviewers and to the medical committees of the CRCC. RESULTS: The principle recommendations concerning the place of radiochemotherapy in the treatment of cancer of the cervix are 1/ the available data shows a significant increase in local control (level of evidence A) and of overall survival (level of evidence B1) following concomitant radiochemotherapy as compared to radiotherapy alone or the combination of radiotherapy-hydroxyurea. For stages IB, IIA, proximal IIB with bad prognostic factors (tumour size greater than 4 cm and/or invasion of pelvic nodes and/or microscopic invasion of the parametrium) and without lumbo-aortic nodal invasion, concomitant radiochemotherapy can be considered as standard treatment. This benefit is less clear for stages distal IIB, III and IVA without para-aortic nodal invasion (level of evidence C) and must be confirmed (expert agreement). 2/ the toxicity of radiochemotherapy is essentially haematologic and gastrointestinal (level of evidence B1) and is greater than that of radiotherapy alone (level of evidence B1). 3/ these results have been obtained by the combination of chemotherapy based oncisplatin alone, or in combination with 5-FU. Although of equal benefit, the toxicity of the cisplatin/5-FU/ hydroxyurea combination was greater than that of cisplatin alone in a trial comparing the two protocols. A significantly longer survival have also been obtained by the combination of chemoradiation and adjuvant chemotherapy with epirubicin (level of evidence C). These results must be confirmed. 4/ the exact means of delivering the chemotherapy has not been clearly established. In fact, in these trials, some protocols use cisplatin weekly at a dose of 40 mg/m2 and others every three or four weeks at doses ranging from 50 to 75 mg/m2. Subsequent randomised studies are likely to establish optimal schema for the delivery of chemotherapy when combined with external radiotherapy and brachytherapy.

Combined Modality Therapy↗