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Even though stress belongs to the most common lifestyle risk factors of cardiovascular diseases, there are only limited data on direct influence of stressors on the heart. The aim of the present study was to explore selected protein signaling pathways in response to repeated immobilization stress in the heart tissue. Effects of simultaneous treatment with atosiban, an oxytocin receptor antagonist, on stress-induced changes in the heart were also investigated. Male Wistar rats were exposed to repeated immobilization (2 h daily, lasting 2 weeks). The results showed increased phosphorylation of Akt kinase, enhanced levels of Bcl-2, and decreased levels of cleaved caspase-3 in the left ventricle in response to chronic stress independently of the treatment. Exposure to restraint led to the rise of HSP-90 and p53 in vehicle-treated rats only. Stress failed to modify MMP-2 activity and ultrastructure of the heart tissue. Treatment with the oxytocin/vasopressin receptor antagonist atosiban reversed stress-induced rise in HSP-90 and p53 proteins. In conclusion, our data demonstrate that repeated restraint stress induces Akt kinase activation and this is associated with elevation of anti-apoptotic proteins (Bcl-2) and down-regulation of pro-apoptotic proteins (cleaved caspase-3). These findings suggest that activation of pro-survival anti-apoptotic Akt kinase pathway plays an important role in molecular mechanisms underlying responses and adaptation of the rat heart to repeated stress exposure. The results further indicate a regulatory role of oxytocin/vasopressin in the control of stress-induced activation in HSP-90 and related proteins. Key words: restraint stress, heart, protein signaling, atosiban. Meme si le stress fait partie des facteurs les plus communs relies au style de vie quant au risque de maladies cardiovasculaires, les donnees relatives a l'influence directe des stresseurs sur le coeur sont limitees. Le but de l'etude presente etait d'explorer des voies de signalisation proteiques selectionnees activees en reponse a une immobilisation repetee dans le tissu cardiaque. Les effets d'un traitement simultane a l'atosiban, un antagoniste du recepteur de l'ocytocine, sur les changements induits par le stress dans le coeur ont aussi ete examines. Des rats Wistar males ont ete exposes a des immobilisations repetees (2 h par jour, pendant 2 semaines). Les resultats ont montre un accroissement de la phosphorylation de la kinase Akt, une augmentation des niveaux de Bcl-2 et une diminution des niveaux de la caspase-3 dans le ventricule gauche, en reponse au stress chronique, independamment du traitement. La soumission a la contention resultait en un accroissement de HSP-90 et p53 chez les rats traites au vehicule seulement. Le stress ne modifiait pas l'activite de MMP-2 ni l'ultrastructure du tissu cardiaque. Le traitement avec l'antagoniste du recepteur de l'ocytocine/vasopressine, l'atosiban, renversait l'accroissement de HSP-90 et de p53 induit par le stress. En conclusion, les donnees des auteurs demontrent que le stress cause par une contention repetee induit l'activation de la kinase Akt et cela est associe a l'elevation des proteines anti-apoptose (Bcl-2) et a regulation a la baisse des proteines pro-apoptose (caspase-3 clivee). Ces donnees suggerent que l'activation de la voie d'Akt pro-survie et anti- apoptose joue un role important dans les mecanismes moleculaires qui sous-tendent les reponses et l'adaptation du coeur de rat a une exposition repetee a un stress. Les resultats indiquent de plus que l'ocytocine/vasopressine joue un role regulateur dans le controle de l'activation induite par le stress de HSP-90 et les proteines qui lui sont reliees. [Traduit par la Redaction] Mots-cles: stress de contention, coeur, signalisation proteique, atosiban., Introduction Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are highly variable and specific depending on the type and nature of the stressors (Jezova and Skultetyova 1997; Jezova [...]

The aim of this study was to verify the presence of metabotropic glutamate receptor subtype 5 (mGluR5) in the adrenal gland of male rats of 2 different strains, and to test the hypothesis that treatment with mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) affects hormone release and adrenal gene expression of mGluR5 under conditions of stress. The results clearly show the gene expression of mGluR5 in the adrenal gland in both the adrenal cortex and medulla. Treatment with the glutamate release inhibitor riluzole (4 mg x [(kg body mass).sup.-1] x [day.sup.-1] for 2 weeks) failed to modify mRNA levels of either the mGluR5 or NR1 subunit of the NMDA receptor in the adrenal glands, as measured by real-time PCR. Blockade of mGluR5 with MPEP (1 mg x [kg.sup.-1] for 4 days) increased corticosterone but not catecholamine release during restraint stress (20 min). Treatment with MPEP had no effect on mRNA levels coding for steroidogenic factors StAR and SF-1, and decreased mGluR5 gene expression in the adrenal gland. In conclusion, mGluR5 is not likely to play a significant role in stress-induced catecholamine release. Pharmacological blockade of mGluR5 has a modest influence on the hypothalamic-pituitary-adrenocortical axis, as reflected in adrenal hypertrophy and increased corticosterone concentrations. Key words: glutamate receptors, stress, adrenal gland, stress hormones, steroidogenic factors. Les objectifs des presentes etudes consistaient a verifier la presence du recepteur du glutamate metabotropique du sous-type 5 (mGluR5) dans la surrenale de rats males appartenant a deux souches differentes, et a tester l'hypothese qu'un traitement avec un antagoniste du mGluR5, la 2-methyl-6-(phenylethynyl)-pyridine (MPEP) a un impact sur la liberation d'hormones et l'expression genique du mGluR5 dans les surrenales en condition de stress. Les resultats demontrent clairement l'expression genique du mGluR5 dans la surrenale, tant dans le cortex que dans la medulla. Un traitement avec un inhibiteur de la liberation de glutamate, le riluzole (4 mg x [(kg de masse corporelle).sup.-1] x [jour.sup.-1] pendant 2 semaines) ne parvenait pas a modifier les niveaux d'ARNm de mGluR5 et de la sous-unite NR1 du recepteur NMDA dans les surrenales, mesures par PCR en temps reel. Le blocage du mGluR5 par la MPEP (1 mg x [kg.sup.-1] pendant 4 jours) augmentait la liberation de corticosterone, contrairement aux catecholamines, durant un stress de contention (20 minutes). Le traitement a la MPEP n'avait pas d'effet sur les niveaux d'ARNm des facteurs steroidogenes StAR et SF-1, et diminuait l'expression genique de mGluR5 dans la surrenale. En conclusion, les recepteurs du glutamate mGluR5 ne jouent probablement pas un role significatif dans la liberation de catecholamines induite par le stress. Le blocage pharmacologique du mGluR5 n'exerce qu'une influence modeste sur l'axe hypothalamo-hypophyso-surrenalien, refletee par une hypertrophie surrenalienne et des concentrations accrues de corticosterone. [Traduit par la Redaction] Mots-cles: recepteurs du glutamate, stress, glande surrenale, hormones de stress, facteurs steroidogenes., Introduction Glutamate is one of neurotransmitters involved in the control of neuroendocrine functions. The involvement of central ionotropic glutamate receptors in the control of the hypothalamic-pituitary-adrenocortical (HPA) axis is well [...]

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β3-adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β3-receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β3-receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β3-adrenergic receptor gene expression in the brain. Greater reduction of β3-adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β3-adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections. [ABSTRACT FROM AUTHOR]

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Even though stress belongs to the most common lifestyle risk factors of cardiovascular diseases, there are only limited data on direct influence of stressors on the heart. The aim of the present study was to explore selected protein signaling pathways in response to repeated immobilization stress in the heart tissue. Effects of simultaneous treatment with atosiban, an oxytocin receptor antagonist, on stress-induced changes in the heart were also investigated. Male Wistar rats were exposed to repeated immobilization (2 h daily, lasting 2 weeks). The results showed increased phosphorylation of Akt kinase, enhanced levels of Bcl-2, and decreased levels of cleaved caspase-3 in the left ventricle in response to chronic stress independently of the treatment. Exposure to restraint led to the rise of HSP-90 and p53 in vehicle-treated rats only. Stress failed to modify MMP-2 activity and ultrastructure of the heart tissue. Treatment with the oxytocin/vasopressin receptor antagonist atosiban reversed stress-induced rise in HSP-90 and p53 proteins. In conclusion, our data demonstrate that repeated restraint stress induces Akt kinase activation and this is associated with elevation of anti-apoptotic proteins (Bcl-2) and down-regulation of pro-apoptotic proteins (cleaved caspase-3). These findings suggest that activation of pro-survival anti-apoptotic Akt kinase pathway plays an important role in molecular mechanisms underlying responses and adaptation of the rat heart to repeated stress exposure. The results further indicate a regulatory role of oxytocin/vasopressin in the control of stress-induced activation in HSP-90 and related proteins. [ABSTRACT FROM AUTHOR]

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.