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No description available.

O subnúcleo póstero-dorsal da amígdala medial (AMePD) de ratos modula comportamentos sociais, como é o reprodutivo, e respostas a estímulos estressantes. Para tanto, são necessários ajustes concomitantes da função cardiovascular. Dada sua notável presença no AMePD, o glutamato (GLU), o ácido δ-aminobutírico (GABA), a ocitocina (OT), a somatostatina (SST) e a angiotensina II (Ang II) poderiam estar envolvidos em tais ajustes homeostáticos. O objetivo deste trabalho foi avaliar o efeito da microinjeção de GLU, GABA, OT, SST e Ang II microinjetados diretamente no AMePD de ratos não anestesiados sobre o controle cardiovascular em situação basal e após estimulação dos barorreceptores e quimiorreceptores. Ratos machos Wistar (3 meses de idade) foram mantidos em condições padrão de biotério e cuidados éticos. Os animais foram anestesiados e submetidos à cirurgia estereotáxica para implantação unilateral de cânula no AMePD, lado direito. No quinto dia pós-cirúrgico, os animais foram novamente anestesiados e submetidos à colocação de cateter de polietileno na luz da artéria aorta abdominal e outro na veia cava inferior. Um dia após a canulação dos vasos, os animais foram microinjetados no AMePD com solução salina (0,3 μl; n = 8), GLU na dose de 2 μg/0,3 μl (n = 7), GABA nas doses de 61 ng/0.3μl (n = 7) e de 100 μg/0.3 μl (n = 7), OT nas doses de 10 ng/0,3 μl (n = 7) e de 25 pg/0,3 μl (n = 6), SST nas doses de 1 μM/0,3μl (n = 8) e de 15 fmol/0,3μl (n = 5) e Ang II nas doses de 50 fmol/0,3 μl (n = 7) e de 50 pmol/0,3 μl (n = 7). Dados de frequência cardíaca (FC) e de pressão arterial (PA) foram registrados por 15 minutos em período basal, controle, e, a seguir, foram microinjetadas as substâncias mencionadas e testadas as variáveis de interesse. Os reflexos pressóricos foram testados pela injeção de fenilefrina (8 μg/ml) e nitroprussiato de sódio (100 μg/ml) e os quimiorreceptores, pela de cianeto de potássio (doses crescentes desde 60 até 180 μg/kg). O modelo autoregressivo de análise espectral e a análise simbólica foram utilizados para avaliar a variabilidade da FC e da PA e as atividades simpática e vagal responsáveis pela variabilidade nos dados registrados. Os dados foram comparados pelo teste da análise da variância (ANOVA) de duas vias para medidas repetidas e pelo teste post hoc de Newman- Keuls ou pela ANOVA de uma via e pelo teste de Tukey, conforme apropriado. O nível de significância estatística foi estabelecido em p < 0,05. Não houve diferença estatística entre os grupos estudados nos valores de FC, PA sistólica, PA diastólica e PA média em situação basal ou após as diferentes microinjeções nos grupos microinjetados com neurotransmissores ou com os neuropeptídeos estudados (p > 0,05). Microinjeções de salina, de GLU (2 μg) ou GABA (61 ng ou 100 μg; n = 7 cada grupo) não afetaram os parâmetros basais ou respostas do quimiorreflexo. Os valores correspondentes à curva da modificação da PAM de acordo com a variação da FC foram estatisticamente diferentes entre os grupos estudados, sendo que a curva após a microinjeção de GABA 61 ng no AMePD foi diferente dos grupos que receberam salina ou GABA na maior dose (100 μg; p < 0,05 em ambos os casos). No que se refere ao platô de taquicardia, a curva de inclinação dos dados referente à sensibilidade média do barorreflexo foi diferente entre os grupos que receberam GLU ou GABA em ambas as doses em comparação com o que recebeu salina (p < 0,01). O GLU aumentou valores índices das análises espectral e simbólica simpáticos relacionados com modulações cardíaca e vascular (P <0,05). A administração de GABA (61 ng) também induziu os maiores valores de variabilidade na FC (P <0,05) que pode ser e associado a uma ativação parassimpática central. No grupo de animais microinjetados com salina, OT (10 ng e 25 pg), SST (1μM e 15 fmol) e Ang II (50 fmol e 50 pmol) no AMePD, os valores mais próximos do basal foram obtidos com a menor dose de KCN (60 μg/kg) e ocorreu, conforme o esperado, uma redução estatisticamente significativa maior na FC quando foram aumentadas as doses injetadas de KCN para 100 μg/kg, 140 μg/kg ou 180 μg/kg (teste de Newman-Keuls, p < 0,001 em todos os casos, quando comparadas com a menor dose injetada). Ang II na dose de 50 pmol microinjetada no AMePD gerou maior diminuição reflexa na FC quando comparado com o grupo controle após a estimulação dos quimiorreceptores com KCN nas doses de 60 e 140 μg/kg (p < 0,05). Ang II na dose de 50 pmol microinjetada no AMePD gerou maior diminuição reflexa na PA quando comparado com o grupo controle após a estimulação dos quimiorreceptores com KCN na dose de 140 μg/kg (p < 0,05). Os valores referentes ao ponto de maior inclinação da curva pressórica referente a respostas geradas pelos barorreceptores, (PA50), após injeções de fenilefrina e nitroprussiato de sódio, foram menores nos ratos que receberam OT na dose de 10 ng ou SST na dose de 1 μM microinjetadas no AMePD, quando comparado ao grupo controle (p < 0,05). Os valores referentes à sensibilidade média do barorreflexo (ganho em bpm/mmHg), após injeções de fenilefrina e nitroprussiato de sódio, foi maior no grupo que recebeu OT na dose de 10 ng quando comparado com a Ang II na dose de 50 pmol. Houve maior variabilidade na PA sistólica, na FC, no componente de baixa e de alta frequência do tacograma e no índice de atividade simpático-vagal da análise espectral nos grupos que receberam OT nas doses de (10 ng e 25 pg), SST (1μM e 15 fmol) e Ang II na dose de 50 pmol (p < 0,05). Tais dados, indicam que o AMePD se vale de sua atividade glutamatérgica, GABAérgica, ocitocinérgica, somatostatinérgica e angiotensinérgica local, por circuitaria própria ou devido a aferências neurais, para modificar variáveis cardiovasculares provavelmente concomitantemente à organização de comportamentos. / The postero-dorsal subnucleus of the medial amygdala (MePD) modulates social behavior of rats, such as reproduction, and responses to stressful stimuli. To this end, concomitants adjustments of the cardiovascular function are modulate. Given its remarkable presence in the MePD, glutamate (GLU), Gamma-amino butyric acid (GABA), oxytocin (OT), somatostatin (SST) and angiotensin II (Ang II) could be involved in such homeostatic adjustments. The objective of this study was to evaluate the effect of microinjection of GLU, GABA, OT, SST and Ang II microinjected directly into the rats MePD on non-anesthetized of cardiovascular control under basal conditions and after stimulation of baroreceptors and chemoreceptors. Male Wistar rats (3 months old) were maintained under standard laboratory conditions and ethical care. The animals were anesthetized and submitted to unilateral stereotactic surgery for implantation of the cannula in the right MePD. On the fifth postoperative day, the animals were again anesthetized and underwent placement of polyethylene catheter in the abdominal aorta and inferior vena cava. One day after the cannulation of the vessels, the animals were microinjected with saline solution, GLU (2 μg/0,3 μl, n = 7), GABA (61 ng/0.3μl, n = 7 and 100 μg/0.3 μl, n = 7), OT (10 ng/0,3 μl, n = 7 and 25 pg/0,3 μl, n = 6), SST (1 μM/0,3μl, n = 8 and 15 fmol/0,3μl, n = 5) and Ang II (50 fmol/0,3 μl, n = 7 and 50 pmol/0,3 μl, n = 7) in the MePD. Data for heart rate (HR) and blood pressure (BP) were recorded for 15 minutes at baseline and then were microinjected the substances aforementioned and tested the variables of interest. Baroreceptor function was tested by phenylephrine (8 μg/ml) and sodium nitroprusside (100 μg/ml) injections. Chemoreflex was tested by potassium cyanide (60 – 180 μg/ml) injections. The autoregressive model of symbolic analysis and spectral analysis were used to evaluate the variability of HR and BP and the sympathetic and vagal activities responsible for variability in the data recorded. The data were compared by a two-way analysis of variance (ANOVA) test for repeated measures and the post hoc Newman-Keuls or an one-way analysis of variance (ANOVA) test for repeated measures and the post hoc Newman-Keuls whenever appropriate. The level of statistical significance was set at P ≤ 0.05. There was no statistical difference between groups in the values of HR, systolic BP, diastolic BP and mean BP at baseline or after microinjections in the different groups (P > 0.05). Microinjections of saline, GLU (2 μg) or GABA (61 ng or 100 μg; n = 7 each group) did not affect the basal or responses the of chemoreflex. The values of the curve of change in the MAP in accordive to the variation of HR, were statistically different between groups, and the curve after the microinjection of GABA 61 ng in the MePD was different in the groups that received saline or the highest GABA dose (100 μg, P < 0.05 in both cases). With regard to the plateau of tachycardia, the slope of the data on the average baroreflex sensitivity was different among the groups receiving GLU or GABA at both doses compared to that received saline (P < 0.01). GLU increased power spectral and symbolic sympathetic indexes related with both cardiac and vascular modulations (P < 0.05). The GABA administration (61 ng, but not 100 μg) also induced higher values of HR variability (P < 0.05), rather associated with a parasympathetic activation. In the group of animals microinjected with saline, OT (10 ng and 25 pg), SST (1μM and 15 fmol) and Ang II (50 fmol and 50 pmol) in MePD, there was as expected, a statistically significant greater reduction in HR increasing when the injected doses of KCN to 100 μg/kg, 140 μg/kg or 180 μg/kg (Newman-Keuls test, P < 0.001 in all cases when compared with the lower injected dose). Ang II at the dose of 50 pmol generated a higher reflex decrease in HR compared to the control group after stimulation of the chemoreceptors with KCN at doses of 60 and 140 μg/kg (P < 0.05). Ang II at the dose of 50 pmol generated a higher reflex decrease in BP compared with the control group after stimulation of the chemoreceptors with KCN at the dose of 140 μg/kg (P < 0.05). The values for the point of greatest slope of the AP response generated by baroreceptors (MAP50) was lower in rats given OT at the dose of 10 ng or SST at the dose of 1 μM compared to the control group (P < 0.05). The average values for the baroreflex sensitivity (gain in bpm/mm Hg) after the injection of phenylephrine and sodium nitroprusside was greater in the group receiving OT at the dose of 10 ng compared with Ang II at the dose of 50 pmol. There was a greater variability in systolic BP, HR, the component of low and high frequency of tachogram and the sympathovagal index studied by spectral analysis in the groups that received OT (10 ng and 25 pg), SST (1 μM and 15 fmol) and Ang II (50 pmol; P < 0.05). These data indicate that the MePD has a glutamatergic, GABAergic, ocitocinergic, somatostatinergic angiotensinergic modulatory activity on cardiovascular response most likely involved in the central organization of behaviors.

O subnúcleo póstero-dorsal da amígdala medial (AMePD) de ratos modula comportamentos sociais, como é o reprodutivo, e respostas a estímulos estressantes. Para tanto, são necessários ajustes concomitantes da função cardiovascular. Dada sua notável presença no AMePD, o glutamato (GLU), o ácido δ-aminobutírico (GABA), a ocitocina (OT), a somatostatina (SST) e a angiotensina II (Ang II) poderiam estar envolvidos em tais ajustes homeostáticos. O objetivo deste trabalho foi avaliar o efeito da microinjeção de GLU, GABA, OT, SST e Ang II microinjetados diretamente no AMePD de ratos não anestesiados sobre o controle cardiovascular em situação basal e após estimulação dos barorreceptores e quimiorreceptores. Ratos machos Wistar (3 meses de idade) foram mantidos em condições padrão de biotério e cuidados éticos. Os animais foram anestesiados e submetidos à cirurgia estereotáxica para implantação unilateral de cânula no AMePD, lado direito. No quinto dia pós-cirúrgico, os animais foram novamente anestesiados e submetidos à colocação de cateter de polietileno na luz da artéria aorta abdominal e outro na veia cava inferior. Um dia após a canulação dos vasos, os animais foram microinjetados no AMePD com solução salina (0,3 μl; n = 8), GLU na dose de 2 μg/0,3 μl (n = 7), GABA nas doses de 61 ng/0.3μl (n = 7) e de 100 μg/0.3 μl (n = 7), OT nas doses de 10 ng/0,3 μl (n = 7) e de 25 pg/0,3 μl (n = 6), SST nas doses de 1 μM/0,3μl (n = 8) e de 15 fmol/0,3μl (n = 5) e Ang II nas doses de 50 fmol/0,3 μl (n = 7) e de 50 pmol/0,3 μl (n = 7). Dados de frequência cardíaca (FC) e de pressão arterial (PA) foram registrados por 15 minutos em período basal, controle, e, a seguir, foram microinjetadas as substâncias mencionadas e testadas as variáveis de interesse. Os reflexos pressóricos foram testados pela injeção de fenilefrina (8 μg/ml) e nitroprussiato de sódio (100 μg/ml) e os quimiorreceptores, pela de cianeto de potássio (doses crescentes desde 60 até 180 μg/kg). O modelo autoregressivo de análise espectral e a análise simbólica foram utilizados para avaliar a variabilidade da FC e da PA e as atividades simpática e vagal responsáveis pela variabilidade nos dados registrados. Os dados foram comparados pelo teste da análise da variância (ANOVA) de duas vias para medidas repetidas e pelo teste post hoc de Newman- Keuls ou pela ANOVA de uma via e pelo teste de Tukey, conforme apropriado. O nível de significância estatística foi estabelecido em p < 0,05. Não houve diferença estatística entre os grupos estudados nos valores de FC, PA sistólica, PA diastólica e PA média em situação basal ou após as diferentes microinjeções nos grupos microinjetados com neurotransmissores ou com os neuropeptídeos estudados (p > 0,05). Microinjeções de salina, de GLU (2 μg) ou GABA (61 ng ou 100 μg; n = 7 cada grupo) não afetaram os parâmetros basais ou respostas do quimiorreflexo. Os valores correspondentes à curva da modificação da PAM de acordo com a variação da FC foram estatisticamente diferentes entre os grupos estudados, sendo que a curva após a microinjeção de GABA 61 ng no AMePD foi diferente dos grupos que receberam salina ou GABA na maior dose (100 μg; p < 0,05 em ambos os casos). No que se refere ao platô de taquicardia, a curva de inclinação dos dados referente à sensibilidade média do barorreflexo foi diferente entre os grupos que receberam GLU ou GABA em ambas as doses em comparação com o que recebeu salina (p < 0,01). O GLU aumentou valores índices das análises espectral e simbólica simpáticos relacionados com modulações cardíaca e vascular (P <0,05). A administração de GABA (61 ng) também induziu os maiores valores de variabilidade na FC (P <0,05) que pode ser e associado a uma ativação parassimpática central. No grupo de animais microinjetados com salina, OT (10 ng e 25 pg), SST (1μM e 15 fmol) e Ang II (50 fmol e 50 pmol) no AMePD, os valores mais próximos do basal foram obtidos com a menor dose de KCN (60 μg/kg) e ocorreu, conforme o esperado, uma redução estatisticamente significativa maior na FC quando foram aumentadas as doses injetadas de KCN para 100 μg/kg, 140 μg/kg ou 180 μg/kg (teste de Newman-Keuls, p < 0,001 em todos os casos, quando comparadas com a menor dose injetada). Ang II na dose de 50 pmol microinjetada no AMePD gerou maior diminuição reflexa na FC quando comparado com o grupo controle após a estimulação dos quimiorreceptores com KCN nas doses de 60 e 140 μg/kg (p < 0,05). Ang II na dose de 50 pmol microinjetada no AMePD gerou maior diminuição reflexa na PA quando comparado com o grupo controle após a estimulação dos quimiorreceptores com KCN na dose de 140 μg/kg (p < 0,05). Os valores referentes ao ponto de maior inclinação da curva pressórica referente a respostas geradas pelos barorreceptores, (PA50), após injeções de fenilefrina e nitroprussiato de sódio, foram menores nos ratos que receberam OT na dose de 10 ng ou SST na dose de 1 μM microinjetadas no AMePD, quando comparado ao grupo controle (p < 0,05). Os valores referentes à sensibilidade média do barorreflexo (ganho em bpm/mmHg), após injeções de fenilefrina e nitroprussiato de sódio, foi maior no grupo que recebeu OT na dose de 10 ng quando comparado com a Ang II na dose de 50 pmol. Houve maior variabilidade na PA sistólica, na FC, no componente de baixa e de alta frequência do tacograma e no índice de atividade simpático-vagal da análise espectral nos grupos que receberam OT nas doses de (10 ng e 25 pg), SST (1μM e 15 fmol) e Ang II na dose de 50 pmol (p < 0,05). Tais dados, indicam que o AMePD se vale de sua atividade glutamatérgica, GABAérgica, ocitocinérgica, somatostatinérgica e angiotensinérgica local, por circuitaria própria ou devido a aferências neurais, para modificar variáveis cardiovasculares provavelmente concomitantemente à organização de comportamentos. / The postero-dorsal subnucleus of the medial amygdala (MePD) modulates social behavior of rats, such as reproduction, and responses to stressful stimuli. To this end, concomitants adjustments of the cardiovascular function are modulate. Given its remarkable presence in the MePD, glutamate (GLU), Gamma-amino butyric acid (GABA), oxytocin (OT), somatostatin (SST) and angiotensin II (Ang II) could be involved in such homeostatic adjustments. The objective of this study was to evaluate the effect of microinjection of GLU, GABA, OT, SST and Ang II microinjected directly into the rats MePD on non-anesthetized of cardiovascular control under basal conditions and after stimulation of baroreceptors and chemoreceptors. Male Wistar rats (3 months old) were maintained under standard laboratory conditions and ethical care. The animals were anesthetized and submitted to unilateral stereotactic surgery for implantation of the cannula in the right MePD. On the fifth postoperative day, the animals were again anesthetized and underwent placement of polyethylene catheter in the abdominal aorta and inferior vena cava. One day after the cannulation of the vessels, the animals were microinjected with saline solution, GLU (2 μg/0,3 μl, n = 7), GABA (61 ng/0.3μl, n = 7 and 100 μg/0.3 μl, n = 7), OT (10 ng/0,3 μl, n = 7 and 25 pg/0,3 μl, n = 6), SST (1 μM/0,3μl, n = 8 and 15 fmol/0,3μl, n = 5) and Ang II (50 fmol/0,3 μl, n = 7 and 50 pmol/0,3 μl, n = 7) in the MePD. Data for heart rate (HR) and blood pressure (BP) were recorded for 15 minutes at baseline and then were microinjected the substances aforementioned and tested the variables of interest. Baroreceptor function was tested by phenylephrine (8 μg/ml) and sodium nitroprusside (100 μg/ml) injections. Chemoreflex was tested by potassium cyanide (60 – 180 μg/ml) injections. The autoregressive model of symbolic analysis and spectral analysis were used to evaluate the variability of HR and BP and the sympathetic and vagal activities responsible for variability in the data recorded. The data were compared by a two-way analysis of variance (ANOVA) test for repeated measures and the post hoc Newman-Keuls or an one-way analysis of variance (ANOVA) test for repeated measures and the post hoc Newman-Keuls whenever appropriate. The level of statistical significance was set at P ≤ 0.05. There was no statistical difference between groups in the values of HR, systolic BP, diastolic BP and mean BP at baseline or after microinjections in the different groups (P > 0.05). Microinjections of saline, GLU (2 μg) or GABA (61 ng or 100 μg; n = 7 each group) did not affect the basal or responses the of chemoreflex. The values of the curve of change in the MAP in accordive to the variation of HR, were statistically different between groups, and the curve after the microinjection of GABA 61 ng in the MePD was different in the groups that received saline or the highest GABA dose (100 μg, P < 0.05 in both cases). With regard to the plateau of tachycardia, the slope of the data on the average baroreflex sensitivity was different among the groups receiving GLU or GABA at both doses compared to that received saline (P < 0.01). GLU increased power spectral and symbolic sympathetic indexes related with both cardiac and vascular modulations (P < 0.05). The GABA administration (61 ng, but not 100 μg) also induced higher values of HR variability (P < 0.05), rather associated with a parasympathetic activation. In the group of animals microinjected with saline, OT (10 ng and 25 pg), SST (1μM and 15 fmol) and Ang II (50 fmol and 50 pmol) in MePD, there was as expected, a statistically significant greater reduction in HR increasing when the injected doses of KCN to 100 μg/kg, 140 μg/kg or 180 μg/kg (Newman-Keuls test, P < 0.001 in all cases when compared with the lower injected dose). Ang II at the dose of 50 pmol generated a higher reflex decrease in HR compared to the control group after stimulation of the chemoreceptors with KCN at doses of 60 and 140 μg/kg (P < 0.05). Ang II at the dose of 50 pmol generated a higher reflex decrease in BP compared with the control group after stimulation of the chemoreceptors with KCN at the dose of 140 μg/kg (P < 0.05). The values for the point of greatest slope of the AP response generated by baroreceptors (MAP50) was lower in rats given OT at the dose of 10 ng or SST at the dose of 1 μM compared to the control group (P < 0.05). The average values for the baroreflex sensitivity (gain in bpm/mm Hg) after the injection of phenylephrine and sodium nitroprusside was greater in the group receiving OT at the dose of 10 ng compared with Ang II at the dose of 50 pmol. There was a greater variability in systolic BP, HR, the component of low and high frequency of tachogram and the sympathovagal index studied by spectral analysis in the groups that received OT (10 ng and 25 pg), SST (1 μM and 15 fmol) and Ang II (50 pmol; P < 0.05). These data indicate that the MePD has a glutamatergic, GABAergic, ocitocinergic, somatostatinergic angiotensinergic modulatory activity on cardiovascular response most likely involved in the central organization of behaviors.

O subnúcleo póstero-dorsal da amígdala medial (AMePD) de ratos modula comportamentos sociais, como é o reprodutivo, e respostas a estímulos estressantes. Para tanto, são necessários ajustes concomitantes da função cardiovascular. Dada sua notável presença no AMePD, o glutamato (GLU), o ácido δ-aminobutírico (GABA), a ocitocina (OT), a somatostatina (SST) e a angiotensina II (Ang II) poderiam estar envolvidos em tais ajustes homeostáticos. O objetivo deste trabalho foi avaliar o efeito da microinjeção de GLU, GABA, OT, SST e Ang II microinjetados diretamente no AMePD de ratos não anestesiados sobre o controle cardiovascular em situação basal e após estimulação dos barorreceptores e quimiorreceptores. Ratos machos Wistar (3 meses de idade) foram mantidos em condições padrão de biotério e cuidados éticos. Os animais foram anestesiados e submetidos à cirurgia estereotáxica para implantação unilateral de cânula no AMePD, lado direito. No quinto dia pós-cirúrgico, os animais foram novamente anestesiados e submetidos à colocação de cateter de polietileno na luz da artéria aorta abdominal e outro na veia cava inferior. Um dia após a canulação dos vasos, os animais foram microinjetados no AMePD com solução salina (0,3 μl; n = 8), GLU na dose de 2 μg/0,3 μl (n = 7), GABA nas doses de 61 ng/0.3μl (n = 7) e de 100 μg/0.3 μl (n = 7), OT nas doses de 10 ng/0,3 μl (n = 7) e de 25 pg/0,3 μl (n = 6), SST nas doses de 1 μM/0,3μl (n = 8) e de 15 fmol/0,3μl (n = 5) e Ang II nas doses de 50 fmol/0,3 μl (n = 7) e de 50 pmol/0,3 μl (n = 7). Dados de frequência cardíaca (FC) e de pressão arterial (PA) foram registrados por 15 minutos em período basal, controle, e, a seguir, foram microinjetadas as substâncias mencionadas e testadas as variáveis de interesse. Os reflexos pressóricos foram testados pela injeção de fenilefrina (8 μg/ml) e nitroprussiato de sódio (100 μg/ml) e os quimiorreceptores, pela de cianeto de potássio (doses crescentes desde 60 até 180 μg/kg). O modelo autoregressivo de análise espectral e a análise simbólica foram utilizados para avaliar a variabilidade da FC e da PA e as atividades simpática e vagal responsáveis pela variabilidade nos dados registrados. Os dados foram comparados pelo teste da análise da variância (ANOVA) de duas vias para medidas repetidas e pelo teste post hoc de Newman- Keuls ou pela ANOVA de uma via e pelo teste de Tukey, conforme apropriado. O nível de significância estatística foi estabelecido em p < 0,05. Não houve diferença estatística entre os grupos estudados nos valores de FC, PA sistólica, PA diastólica e PA média em situação basal ou após as diferentes microinjeções nos grupos microinjetados com neurotransmissores ou com os neuropeptídeos estudados (p > 0,05). Microinjeções de salina, de GLU (2 μg) ou GABA (61 ng ou 100 μg; n = 7 cada grupo) não afetaram os parâmetros basais ou respostas do quimiorreflexo. Os valores correspondentes à curva da modificação da PAM de acordo com a variação da FC foram estatisticamente diferentes entre os grupos estudados, sendo que a curva após a microinjeção de GABA 61 ng no AMePD foi diferente dos grupos que receberam salina ou GABA na maior dose (100 μg; p < 0,05 em ambos os casos). No que se refere ao platô de taquicardia, a curva de inclinação dos dados referente à sensibilidade média do barorreflexo foi diferente entre os grupos que receberam GLU ou GABA em ambas as doses em comparação com o que recebeu salina (p < 0,01). O GLU aumentou valores índices das análises espectral e simbólica simpáticos relacionados com modulações cardíaca e vascular (P <0,05). A administração de GABA (61 ng) também induziu os maiores valores de variabilidade na FC (P <0,05) que pode ser e associado a uma ativação parassimpática central. No grupo de animais microinjetados com salina, OT (10 ng e 25 pg), SST (1μM e 15 fmol) e Ang II (50 fmol e 50 pmol) no AMePD, os valores mais próximos do basal foram obtidos com a menor dose de KCN (60 μg/kg) e ocorreu, conforme o esperado, uma redução estatisticamente significativa maior na FC quando foram aumentadas as doses injetadas de KCN para 100 μg/kg, 140 μg/kg ou 180 μg/kg (teste de Newman-Keuls, p < 0,001 em todos os casos, quando comparadas com a menor dose injetada). Ang II na dose de 50 pmol microinjetada no AMePD gerou maior diminuição reflexa na FC quando comparado com o grupo controle após a estimulação dos quimiorreceptores com KCN nas doses de 60 e 140 μg/kg (p < 0,05). Ang II na dose de 50 pmol microinjetada no AMePD gerou maior diminuição reflexa na PA quando comparado com o grupo controle após a estimulação dos quimiorreceptores com KCN na dose de 140 μg/kg (p < 0,05). Os valores referentes ao ponto de maior inclinação da curva pressórica referente a respostas geradas pelos barorreceptores, (PA50), após injeções de fenilefrina e nitroprussiato de sódio, foram menores nos ratos que receberam OT na dose de 10 ng ou SST na dose de 1 μM microinjetadas no AMePD, quando comparado ao grupo controle (p < 0,05). Os valores referentes à sensibilidade média do barorreflexo (ganho em bpm/mmHg), após injeções de fenilefrina e nitroprussiato de sódio, foi maior no grupo que recebeu OT na dose de 10 ng quando comparado com a Ang II na dose de 50 pmol. Houve maior variabilidade na PA sistólica, na FC, no componente de baixa e de alta frequência do tacograma e no índice de atividade simpático-vagal da análise espectral nos grupos que receberam OT nas doses de (10 ng e 25 pg), SST (1μM e 15 fmol) e Ang II na dose de 50 pmol (p < 0,05). Tais dados, indicam que o AMePD se vale de sua atividade glutamatérgica, GABAérgica, ocitocinérgica, somatostatinérgica e angiotensinérgica local, por circuitaria própria ou devido a aferências neurais, para modificar variáveis cardiovasculares provavelmente concomitantemente à organização de comportamentos. / The postero-dorsal subnucleus of the medial amygdala (MePD) modulates social behavior of rats, such as reproduction, and responses to stressful stimuli. To this end, concomitants adjustments of the cardiovascular function are modulate. Given its remarkable presence in the MePD, glutamate (GLU), Gamma-amino butyric acid (GABA), oxytocin (OT), somatostatin (SST) and angiotensin II (Ang II) could be involved in such homeostatic adjustments. The objective of this study was to evaluate the effect of microinjection of GLU, GABA, OT, SST and Ang II microinjected directly into the rats MePD on non-anesthetized of cardiovascular control under basal conditions and after stimulation of baroreceptors and chemoreceptors. Male Wistar rats (3 months old) were maintained under standard laboratory conditions and ethical care. The animals were anesthetized and submitted to unilateral stereotactic surgery for implantation of the cannula in the right MePD. On the fifth postoperative day, the animals were again anesthetized and underwent placement of polyethylene catheter in the abdominal aorta and inferior vena cava. One day after the cannulation of the vessels, the animals were microinjected with saline solution, GLU (2 μg/0,3 μl, n = 7), GABA (61 ng/0.3μl, n = 7 and 100 μg/0.3 μl, n = 7), OT (10 ng/0,3 μl, n = 7 and 25 pg/0,3 μl, n = 6), SST (1 μM/0,3μl, n = 8 and 15 fmol/0,3μl, n = 5) and Ang II (50 fmol/0,3 μl, n = 7 and 50 pmol/0,3 μl, n = 7) in the MePD. Data for heart rate (HR) and blood pressure (BP) were recorded for 15 minutes at baseline and then were microinjected the substances aforementioned and tested the variables of interest. Baroreceptor function was tested by phenylephrine (8 μg/ml) and sodium nitroprusside (100 μg/ml) injections. Chemoreflex was tested by potassium cyanide (60 – 180 μg/ml) injections. The autoregressive model of symbolic analysis and spectral analysis were used to evaluate the variability of HR and BP and the sympathetic and vagal activities responsible for variability in the data recorded. The data were compared by a two-way analysis of variance (ANOVA) test for repeated measures and the post hoc Newman-Keuls or an one-way analysis of variance (ANOVA) test for repeated measures and the post hoc Newman-Keuls whenever appropriate. The level of statistical significance was set at P ≤ 0.05. There was no statistical difference between groups in the values of HR, systolic BP, diastolic BP and mean BP at baseline or after microinjections in the different groups (P > 0.05). Microinjections of saline, GLU (2 μg) or GABA (61 ng or 100 μg; n = 7 each group) did not affect the basal or responses the of chemoreflex. The values of the curve of change in the MAP in accordive to the variation of HR, were statistically different between groups, and the curve after the microinjection of GABA 61 ng in the MePD was different in the groups that received saline or the highest GABA dose (100 μg, P < 0.05 in both cases). With regard to the plateau of tachycardia, the slope of the data on the average baroreflex sensitivity was different among the groups receiving GLU or GABA at both doses compared to that received saline (P < 0.01). GLU increased power spectral and symbolic sympathetic indexes related with both cardiac and vascular modulations (P < 0.05). The GABA administration (61 ng, but not 100 μg) also induced higher values of HR variability (P < 0.05), rather associated with a parasympathetic activation. In the group of animals microinjected with saline, OT (10 ng and 25 pg), SST (1μM and 15 fmol) and Ang II (50 fmol and 50 pmol) in MePD, there was as expected, a statistically significant greater reduction in HR increasing when the injected doses of KCN to 100 μg/kg, 140 μg/kg or 180 μg/kg (Newman-Keuls test, P < 0.001 in all cases when compared with the lower injected dose). Ang II at the dose of 50 pmol generated a higher reflex decrease in HR compared to the control group after stimulation of the chemoreceptors with KCN at doses of 60 and 140 μg/kg (P < 0.05). Ang II at the dose of 50 pmol generated a higher reflex decrease in BP compared with the control group after stimulation of the chemoreceptors with KCN at the dose of 140 μg/kg (P < 0.05). The values for the point of greatest slope of the AP response generated by baroreceptors (MAP50) was lower in rats given OT at the dose of 10 ng or SST at the dose of 1 μM compared to the control group (P < 0.05). The average values for the baroreflex sensitivity (gain in bpm/mm Hg) after the injection of phenylephrine and sodium nitroprusside was greater in the group receiving OT at the dose of 10 ng compared with Ang II at the dose of 50 pmol. There was a greater variability in systolic BP, HR, the component of low and high frequency of tachogram and the sympathovagal index studied by spectral analysis in the groups that received OT (10 ng and 25 pg), SST (1 μM and 15 fmol) and Ang II (50 pmol; P < 0.05). These data indicate that the MePD has a glutamatergic, GABAergic, ocitocinergic, somatostatinergic angiotensinergic modulatory activity on cardiovascular response most likely involved in the central organization of behaviors.

L’objectif de cette thèse a été d’analyser l’effet de l’exercice physique réalisé sur plateforme vibrante (whole-body vibration, WBV) sur l’activité musculaire des membres inférieurs, de développer des outils d’analyse méthodologiques et de proposer des recommandations pratiques d’utilisation. Deux études méthodologiques ont été menées pour identifier la méthode optimale permettant de traiter les signaux d'électromyographie de surface (sEMG) recueillis pendant la vibration et d'analyser l'influence de la méthode de normalisation de l'activité sEMG. Une troisième étude visait à mieux comprendre si les pics sEMG observés dans le spectre de puissance du signal contiennent des artéfacts de mouvement et/ou de l'activité musculaire réflexe. Les trois études suivantes avaient pour but de quantifier l’effet de la WBV sur l’activité musculaire en fonction de différents paramètres tels que, la fréquence de vibration, l'amplitude de la plateforme, une charge supplémentaire, le type de plateforme, l'angle articulaire du genou, et la condition physique du sujet. En outre, l'objectif a été de déterminer l'accélération verticale minimale permettant de stimuler au mieux l'activité musculaire des membres inférieurs. En résumé, les recherches menées au cours de cette thèse fournissent des solutions pour de futures études sur : i) comment supprimer les pics dans le spectre du signal sEMG et, ii) comment normaliser l'activité musculaire pendant un exercice WBV. Enfin, les résultats de cette thèse apportent à la littérature scientifique de nouvelles recommandations pratiques liées à l’utilisation des plateformes vibrantes à des fins d’exercice physique. / The aim of this thesis was to analyze the effect of whole-body vibration (WBV) exercise on lower limb muscle activity and to give methodological implications and practical applications. Two methodological studies were conducted that served to evaluate the optimal method to process the surface electromyography (sEMG) signals during WBV exercise and to analyze the influence of the normalization method on the sEMG activity. A third study aimed to gain insight whether the isolated spikes in the sEMG spectrum contain motion artifacts and/or reflex activity. The subsequent three investigations aimed to explore how the muscle activity is affected by WBV exercise, with a particular focus on the vibration frequency, platform amplitude, additional loading, platform type, knee flexion angle, and the fitness status of the WBV user. The final goal was to evaluate the minimal required vertical acceleration to stimulate the muscle activity of the lower limbs. In summary, the research conducted for this thesis provides implication for future investigations on how to delete the excessive spikes in the sEMG spectrum and how to normalize the sEMG during WBV. The outcomes of this thesis add to the current literature in providing practical applications for exercising on a WBV platform.

Schwankungen des arteriellen Blutdrucks (BP) im niederfrequenten Bereich (LF, 0.02-0.2 Hz) sind möglicherweise Ausdruck von endokrinen Regulationssystemen bei der Aufrechterhaltung der kardiovaskulären Homöostase, wie beispielsweise des Renin-Angiotensin-Systems (RAS). Bei Untersuchungen an Ratten mit sogenannter "one-clip, two-kidney" (1C-2K) Goldblatt Hypertonie wurde ein Anstieg der LF Komponente des BP-Powerspektrums unter aktiviertem RAS gefunden. Trotz der bisherigen Untersuchungen blieb jedoch die Frage ungeklärt, ob dieser Anstieg LF(BP)-Power auf einer Stimulation des RAS beruht, oder durch die Blutdruckerhöhung selbst bedingt ist. Aus diesem Grund wurden die Auswirkungen eines stimulierten RAS auf BP-Oszillationen im LF-Bereich in dieser Studie untersucht, während ein Blutdruckanstieg pharmakologisch verhindert wurde. Zweiundzwanzig normotensive Wistar- und siebzehn normotensive Brown-Norway-Katholiek-Ratten wurden aus diesem Grunde chronisch mit einem Telemetriesender instrumentiert. Es erfolgten Blutentnahmen zur Reninaktivitsbestimmung, der BP wurde jeden zweiten Tag telemetrisch aufgezeichnet. Nach drei Wochen wurden die Tiere in zwei Behandlungsgruppen aufgeteilt. Entweder wurden die Tiere einer Behandlung mit Placebo zugewiesen (n=14 bei den Wistar-Ratten und n=8 bei den Brown-Norway-Katholiek-Ratten), oder sie erhielten eine Behandlung mit Hydralazin (n=8 bei den Wistar-Ratten und n=9 bei den Brown-Norway-Katholiek-Ratten, 40-120 mg/kg/Tag). Ein Silberclip (innerer Durchmesser 200 Mikrometer) wurde auf die linke Nierenarterie plaziert, eine erneute Blutentnahme erfolgte und der BP wurde für weitere drei Wochen gemessen. Hiernach wurde die Behandlung beendet, der Clip von der Nierenarterie entfernt und eine letzte Blutabnahme erfolgte. Abschließende Blutdruck-Registrierungen wurden über einen Zeitraum von drei Wochen durchgeführt. Die Power im LF-Bereich wurde aus den aufgezeichneten Blutdrucksignalen berechnet. Nach Implantation eines Nierenclips stieg der BP bei den mit Placebo behandelten Tieren signifikant an (+37 +/- 5.7 mmHg bei den Wistar-Ratten und +50 +/- 7.4 mmHg bei den Brown-Norway-Katholiek-Ratten, p / Low frequency (LF, 0.02-0.2 Hz) blood pressure (BP) fluctuations may result from cardiovascular regulation by endocrine systems such as the renin-angiotensin system (RAS). Studies employing one-clip, two-kidney (1C-2K) Goldblatt hypertension in rats demonstrated an increase in the LF component of the BP power spectrum. However it remains controversial, whether this increase in LF(BP)-Power is due to the stimulation of the RAS or to the elevation in BP itself. Therefore, we investigated the effect of RAS stimulation on LF(BP) fluctuation while the increase in BP was prevented pharmacologically. Twenty-two normotensive Wistar and seventeen Brown-Norway Katholiek rats were chronically instrumented with telemetric BP sensors, blood samples for measurement of the renin activity were taken and BP was monitored every other day. Three weeks later, rats were subjected to oral treatment with either placebo (n=14 in the Wistar rats and n=8 in the Brown-Norway Katholiek rats) or hydralazine (n=8 in the Wistar rats and n=9 in the Brown-Norway Katholiek rats, 40-120 mg/kg/day). A stainless steel clip (inner diameter 200 micrometer) was placed on the left renal artery, again blood samples were taken and BP was recorded for another three weeks. Finally, treatment was discontinued, the clip was removed from the renal artery, a last blood sample was taken and BP was monitored for a final period of three weeks. LF spectral power was calculated off-line from the recorded BP signal. After renal artery clipping BP significantly increased in placebo-treated rats (+37 +/- 5.7 mmHg in the Wistar rats, +50 +/- 7.4 mmHg in the Brown-Norway Katholiek rats, p

Diese Dissertation ist ein Beitrag zum Forschungsfeld der Stressökologie, im Spe-ziellen der Verhaltensökotoxikologie. Das spontane lokomotorische Verhalten der Fischarten Danio rerio und Leucaspius delineatus wurde unter sublethaler Expo-sition mit dem Cyanobakterientoxin Microcystin-LR (MC-LR) und dem Xenobio-tikums 2.4.4`-Trichlorobiphenyl (PCB 28) quantifiziert. Die Schwimmgeschwin-digkeit und Anzahl der Wendungen wurden kontinuierlich mit einem automati-schen Video-Monitoringsystem unter Laborbedingungen aufgezeichnet. In Hin-blick auf zyklische Aspekte wurden die Verhaltensanalysen mit chronobiologi-schen Methoden kombiniert. Hiermit wurde gezeigt, dass MC-LR und PCB 28 zu signifikanten Effekten in Verhalten und Aktivitätsrhythmik beider Fischarten führten. Höhere Konzentrati-onen beider Untersuchungssubstanzen verursachten eine deutliche Aktivitätsredu-zierung bei Danio rerio und Leucaspius delineatus. Einige der festgestellten Do-sis-Wirkungsbeziehungen entsprechen der Hormesistheorie, z. B. war bei geringe-ren MC-LR Konzentrationen ein Aktivitätsanstieg und bei höheren ein Aktivitäts-abfall beider Fischarten zu verzeichnen. Die Exposition mit MC-LR und PCB 28 verringerte bei beiden Testfischarten die Synchronisation der Aktivität mit dem Zeitgeber Licht. Dies führte bei beiden Fischarten zu einer Phasenverschiebung. Bei Leucaspius delineatus war unter dem Einfluss von MC-LR eine Phasenumkehr zu verzeichnen, die Fische wechselten von Tag- zu Nachtaktivität. Die Cosinor Analyse zeigte Dosis abhängige Veränderungen der circadianen Rhythmen der Schwimmaktivität (z.B. MESOR, Akrophase) unter Einfluss von MC-LR und PCB 28 an. Die Power Spektral Analyse indizierte für beide Fischar-ten unter Einwirkung von MC-LR and PCB 28 eine reduzierte Dominanz des cir-cadianen Rhythmuspeaks. Da die registrierten Unterschiede in der Reaktion beider Fischarten auf MC-LR und PCB 28 eher gering waren, sind Ergebnisse der Art Danio rerio, die häufig in Toxizitätstests verwendet wird, mit denen der einheimischen Art Leucaspius deli-neatus vergleichbar. Die Ergebnisse belegen, dass Verhaltensuntersuchungen in Kombination mit chronobiologischen Auswertemethoden eine sensitive und zuverlässige Abschät-zung des Gefährdungspotentials von Substanzen sowohl auf dem Gebiet der Öko-toxikologie als auch für Biomonitoring ermöglichen. / This thesis contributes to the field of stress ecology specifically behavioural ecotoxicology. The spontaneous locomotor behavior of two fish species Danio re-rio and Leucaspius delineatus was recorded and quantified continuously under sublethal exposure to the cyanotoxin microcystin-LR (MC-LR) and the xenobioti-cum 2.4.4`-trichlorobiphenyl (PCB 28). By using an automated video-monitoring system, the swimming velocity and the number of turns were assessed under labo-ratory conditions. For analysing cyclic aspects basic behavioural analyses were combined with chronobiological procedures as cosinor analysis and power spec-tral analysis. Both MC-LR and PCB 28 acted as stressors and caused significant changes in the behaviour and circadian activity rhythms of Danio rerio as well as Leucaspius de-lineatus. So for both species elevated concentrations of the stressors led to a re-duction of their activity. Some dose-responses correspond to the hormesis theory, e.g., there was an increase of daytime activity at lower MC-LR concentrations and a decrease at elevated concentrations of MC-LR for both species. A degree of desynchronisation of activity to the zeitgeber light, which led to a phase shift was caused by the chemicals in both fish species. In Leucaspius de-lineatus this shift was so drastic that this species reversed their significant diurnal activity and became nocturnal under the influence of MC-LR. The Cosinor analysis revealed MC-LR- and PCB 28-induced, dose-dependent al-terations of the circadian rhythms of activity (e.g., MESOR, acrophase). The power spectral analysis showed that the dominance of the circadian rhythmic peak (of 24 h) was reduced under MC-LR and PCB 28 for both species. Since the observed differences in the reactions of both species to MC-LR and PCB 28 were rather small, the results of the species Danio rerio which is widely used for environmental risk assessment tests, are comparable to those of the native European species Leucaspius delineatus. The findings of this study proved that the basic behavioural analyses combined with chronobiological procedures could be valuable tools for the study of stressful or even harmful environmental factors in the field of ecotoxicology as well as for biomonitoring.