Haemodynamic effects of hypothalamic disconnection in anaesthetized rats

The aim of the present study was to analyse the haemodynamic effects induced by the hypothalamic disconnection (HD) caudal or rostral to the paraventricular nucleus of the hypothalamus (PVN). Mean arterial pressure (MAP), hindlimb, renal and mesenteric blood flow and vascular conductance (HVC, RVC and MVC, respectively) were measured in urethane (1.2 g/kg, i.v.) anesthetized rats for 60 min after disconnection. HD caudal to the PVN was performed with a double-edged microknife of bayonet shape (R=1 mm, H=2 mm) stereotaxically placed, lowered 2.8 mm caudal to the bregma along the midline. The cut was achieved by rotating the microknife 90° right and 90° left. HD rostral to the PVN was performed with the knife placed 0.8 mm caudal to the bregma. Thirty minutes after the hypothalamic disconnection caudal (HD-C), a decrease in MAP was observed (-14±3 mm Hg), reaching a 60-min decrease of 30±3 mm Hg. Hindlimb conductance increased 10 min after HD (156±14%) and remained elevated throughout the experimental period. On the contrary, we observed a transitory renal vasoconstriction (82±9%, ≤20 min) and a late mesenteric vasodilation, starting at 30 min (108±4%) and reaching 138±6% at 60 min. In rats with HD rostral to the PVN, we only observed minor changes in the cardiovascular parameters. In the MAP, there was a slight decrease 60 min after the hypothalamic disconnection rostral (HD-R) (-9±4 mm Hg). There were no significant changes in HVC. RVC and MVC were increased 60 min after the HD-R (116±12% and 124±11%, respectively). These results suggest that vasodilation in the hindlimb and in the mesenteric bed could contribute to the observed decrease in MAP in HD caudal to PVN rats. © 2002 Elsevier Science B.V. All rights reserved.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

Objective - We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. Methods - Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-μl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. Results - Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. Conclusion - MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Paraventricular nucleus of the hypothalamus glutamate neurotransmission modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats

In the present study, the involvement of paraventricular nucleus of the hypothalamus (PVN) glutamate receptors in the modulation of autonomic (arterial blood pressure, heart rate and tail skin temperature) and neuroendocrine (plasma corticosterone) responses and behavioral consequences evoked by the acute restraint stress in rats was investigated. The bilateral microinjection of the selective non-NMDA glutamate receptor antagonist NBQX (2 nmol/ 100 nL) into the PVN reduced the arterial pressure increase as well as the fall in the tail cutaneous temperature induced by the restraint stress, without affecting the stress-induced tachycardiac response. On the other hand, the pretreatment of the PVN with the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) was able to increase the stress-evoked pressor and tachycardiac response, without affecting the fall in the cutaneous tail temperature. The treatment of the PVN with LY235959 also reduced the increase in plasma corticosterone levels during stress and inhibited the anxiogenic-like effect observed in the elevated plus-maze 24 h after the restraint session. The present results show that NMDA and non-NMDA receptors in the PVN differently modulate responses associated to stress. The PVN glutamate neurotransmission, via non-NMDA receptors, has a facilitatory influence on stress-evoked autonomic responses. On the other hand, the present data point to an inhibitory role of PVN NMDA receptors on the cardiovascular responses to stress. Moreover, our findings also indicate an involvement of PVN NMDA glutamate receptors in the mediation of the plasma corticosterone response as well as in the delayed emotional consequences induced by the restraint stress. © 2012 Elsevier B.V. and ECNP.

Involvement of N-methyl-d-aspartate glutamate receptor and nitric oxide in cardiovascular responses to dynamic exercise in rats

Dynamic exercise evokes sustained cardiovascular responses, which are characterized by arterial pressure and heart rate increases. Although it is well accepted that there is central nervous system mediation of cardiovascular adjustments during exercise, information on the role of neural pathways and signaling mechanisms is limited. It has been reported that glutamate, by acting on NMDA receptors, evokes the release of nitric oxide through activation of neuronal nitric oxide synthase (nNOS) in the brain. In the present study, we tested the hypothesis that NMDA receptors and nNOS are involved in cardiovascular responses evoked by an acute bout of exercise on a rodent treadmill. Moreover, we investigated possible central sites mediating control of responses to exercise through the NMDA receptor-nitric oxide pathway. Intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK-801) reduced both the arterial pressure and heart rate increase evoked by dynamic exercise. Intraperitoneal treatment with the preferential nNOS inhibitor 7-nitroindazole reduced exercise-evoked tachycardiac response without affecting the pressor response. Moreover, treadmill running increased NO formation in the medial prefrontal cortex (MPFC), bed nucleus of the stria teminalis (BNST) and periaqueductal gray (PAG), and this effect was inhibited by systemic pretreatment with MK-801. Our findings demonstrate that NMDA receptors and nNOS mediate the tachycardiac response to dynamic exercise, possibly through an NMDA receptor-NO signaling mechanism. However, NMDA receptors, but not nNOS, mediate the exercise-evoked pressor response. The present results also provide evidence that MPFC, BNST and PAG may modulate physiological adjustments during dynamic exercise through NMDA receptor-NO signaling. © 2013 Elsevier B.V.

Inhibitory mechanism of the nucleus of the solitary tract involved in the control of cardiovascular, dipsogenic, hormonal, and renal responses to hyperosmolality

The nucleus of the solitary tract (NTS) is the primary site of visceral afferents to the central nervous system. In the present study, we investigated the effects of lesions in the commissural portion of the NTS (commNTS) on the activity of vasopressinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, plasma vasopressin, arterial pressure, water intake, and sodium excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats with 15-20 days of sham or electrolytic lesion (1 mA; 10 s) of the commNTS were used. CommNTS lesions enhanced a 2 M NaCl intragastrically induced increase in the number of vasopressinergic neurons expressing c-Fos in the PVN (28 ± 1, vs. sham: 22 ± 2 c-Fos/AVP cells) and SON (26 ± 4, vs. sham: 11 ± 1 c-Fos/AVP cells), plasma vasopressin levels (21 ± 8, vs. sham: 6.6 ± 1.3 pg/ml), pressor responses (25 ± 7 mmHg, vs. sham: 7 ± 2 mmHg), water intake (17.5 ± 0.8, vs. sham: 11.2 ± 1.8 ml/2 h), and natriuresis (4.9 ± 0.8, vs. sham: 1.4 ± 0.3 meq/1 h). The pretreatment with vasopressin antagonist abolished the pressor response to intragastric 2 M NaCl in commNTS-lesioned rats (8 ± 2.4 mmHg at 10 min), suggesting that this response is dependent on vasopressin secretion. The results suggest that inhibitory mechanisms dependent on commNTS act to limit or counterbalance behavioral, hormonal, cardiovascular, and renal responses to an acute increase in plasma osmolality. © 2013 the American Physiological Society.

Política pública e avaliação no Brasil: uma interpretação da avaliação do livro didático de geografia para o ensino fundamental

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeitos da expansão de volume extracelular sobre o conteúdo de catecolaminas e a ativação neuronal de estruturas do hipotálamo e do tronco cerebral de ratos

A regulação fina do volume e osmolaridade dos líquidos corporais é fundamental para a sobrevivência. Qualquer variação na composição do meio interno ativa mecanismos comportamentais, neurais e hormonais compensatórios que controlam a ingestão e excreção de água e eletrólitos a fim de manter a homeostase hidroeletrolítica. Alterações na faixa de 1-2% na osmolaridade sanguínea estimulam a liberação de arginina vasopressina (AVP) que resulta em antidiurese além de ocitocina (OT) e peptídeo natriurético atrial (ANP) que promovem a natriurese. Trabalhos realizados em nosso laboratório utilizando o modelo experimental de expansão do volume extracelular (EVEC) mostraram ativação de neurônios magnocelulares ocitocinérgicos localizados no núcleo paraventricular (PVN) e núcleo supra-óptico (SON) responsáveis pela secreção de OT e AVP, igualmente alteradas em resposta a este estímulo. A participação do sistema nervoso simpático nestas condições tem sido levantada. Projeções medulares e tronco-encefálicas (simpáticas) para o hipotálamo poderiam atuar de forma seletiva inibindo sinalizações para a ingestão e estimulando sinalizações para excreção de água e eletrólitos. O papel de vias noradrenérgicas tronco-encefálicas nesta regulação ainda precisa ser mais bem estabelecido. Assim sendo, objetivamos neste estudo esclarecer o papel do sistema nervoso simpático (via noradrenérgicas) na regulação das alterações induzidas pelo modelo de EVEC, analisando por cromatografia líquida de alta eficácia o conteúdo de noradrenalina (NA), adrenalina (AD) e serotonina (5-HT) em estruturas do tronco cerebral como núcleo do trato solitário (NTS), bulbo rostro-ventro lateral (RVLM), locus coeruleus (LC) e núcleo dorsal da rafe (NDR) e estruturas hipotalâmicas como SON e PVN. Procuramos ainda, através de estudos imunocitoquímicos determinar alterações no padrão de ativação neuronal pela análise de Fos-TH ou Fos-5HT nas estruturas acima mencionadas em condições experimentais nas quais são induzidas alterações do volume do líquido extracelular.

A atuação do sistema interamericano de proteção dos Direitos Humanos na defesa dos direitos econômicos, sociais e culturais

A presente Tese de Doutorado tem por objetivo estudar a atuação dos órgãos do Sistema Interamericano de Direitos Humanos no que se refere à proteção e à promoção dos direitos econômicos, sociais e culturais. Para tanto, a pesquisa parte de considerações acerca do que seriam tais direitos, analisando e refutando teorias e concepções que tentaram recusá-los enquanto normas de Direitos Humanos, o que teria motivado a elaboração de dispositivos normativos vagos e a ausência de mecanismos de monitoramento de igual forma, como havia sido previsto para o rol do grupo de Direitos Humanos, denominado de direitos civis e políticos. A fim de demonstrar que os direitos econômicos, sociais e culturais fazem parte de um grupo de direitos plenamente justiciáveis, a tese também analisa elementos que comumente são conferido-lhes, como progressividade, proibição de retrocesso, aplicação do máximo de recursos disponíveis e núcleo mínimo de direitos, a partir do que é desenvolvido pelo Comitê de Direitos Econômicos, Sociais e Culturais da Organização das Nações Unidas, para, posteriormente, apresentar como enfrentam tais aspectos, os órgãos do Sistema Interamericano. Do estudo de normas internacionais e do sistema internacional de monitoramento, que foram especialmente construídos para os direitos econômicos, sociais e culturais, verificam-se diversos níveis de obrigações jurídicas, do que se propõe uma classificação para os diferentes mecanismos de acesso ao Sistema de Proteção dos Direitos Humanos Regional, os quais podem ser direcionados à tutela de um órgão jurisdicional ou quase-judicial, ou mesmo por outros meios que também promovam tais direitos e possibilitem sua reparação em caso de violação. Os diferentes mecanismos são utilizados pelos órgãos do Sistema Interamericano para tutelar os direitos econômicos, sociais e culturais. Dada a sua importância, Comissão e Corte Interamericanas de Direitos Humanos foram estudadas pela presente pesquisa, atribuindo-se enfoque a sua atuação para proteção dos direitos em tela, bem como sobre as recentes modificações das suas funções e ritos processuais.

Detecção microbiológica e molecular de Staphylococcus aureus em amostras de leite bovino obidas de tanques de expansão-correlação com a presença de resíduos de antibióticos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ajustes cardiovasculares e do equilibrio hidroeletrolítico induzidos por soluções hipertônicas em ratos com lesão do núcleo do trato solitário comissural

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Transcription Factor CREB3L1 Regulates Vasopressin Gene Expression in the Rat Hypothalamus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A aposentadoria por idade do trabalhador rural sob o enfoque constitucional: efetivação por meio da atividade judicial

Pós-graduação em Direito - FCHS

Hydrogen peroxide attenuates the dipsogenic, renal and pressor responses induced by cholinergic activation of the medial septal area

Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis, antidiuresis and pressor response. In the brain, hydrogen peroxide (H2O2) modulates autonomic and behavioral responses. In the present study, we investigated the effects of the combination of carbachol and H2O2 injected into the MSA on water intake, renal excretion, cardiovascular responses and the activity of vasopressinergic and oxytocinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Furthermore, the possible modulation of carbachol responses by H2O2 acting through K+ATP channels was also investigated. Male Holtzman rats (280–320 g) with stainless steel cannulas implanted in the MSA were used. The pre-treatment with H2O2 in the MSA reduced carbachol-induced thirst (7.9 ± 1.0, vs. carbachol: 13.2 ± 2.0 ml/60 min), antidiuresis (9.6 ± 0.5, vs. carbachol: 7.0 ± 0.8 ml/120 min,), natriuresis (385 ± 36, vs. carbachol: 528 ± 46 μEq/120 min) and pressor response (33 ± 5, vs. carbachol: 47 ± 3 mmHg). Combining H2O2 and carbachol into the MSA also reduced the number of vasopressinergic neurons expressing c-Fos in the PVN (46.4 ± 11.2, vs. carbachol: 98.5 ± 5.9 c-Fos/AVP cells) and oxytocinergic neurons expressing c-Fos in the PVN (38.5 ± 16.1, vs. carbachol: 75.1 ± 8.5 c-Fos/OT cells) and in the SON (57.8 ± 10.2, vs. carbachol: 102.7 ± 7.4 c-Fos/OT cells). Glibenclamide (K+ATP channel blocker) into the MSA partially reversed H2O2 inhibitory responses. These results suggest that H2O2 acting through K+ATP channels in the MSA attenuates responses induced by cholinergic activation in the same area.

Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Sodium intake, brain c-Fos protein and gastric emptying in cell-dehydrated rats treated with methysergide into the lateral parabrachial nucleus

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)