New insights on amygdala : basomedial amygdala regulates the physiological response to social novelty.

The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These subnuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important. Yet, the involvement of the basomedial amygdala (BMA) in the regulation of emotional states has yet to be defined. Therefore, the aim of our study was to investigate the regulatory role of the BMA on the responses evoked during a social novelty model and whether the regulatory role depended on an interaction with the dorsomedial hypothalamus (DMH). Our results showed that the chemical inhibition of the BMA by the microinjection of muscimol (c-aminobutyric acid (GABAA) agonist) promoted increases in mean arterial pressure (MAP) and heart rate (HR), whereas the chemical inhibition of regions near the BMA did not induce such cardiovascular changes. In contrast, the BMA chemical activation by the bilateral microinjection of bicuculline methiodide (BMI; GABAA antagonist), blocked the increases in MAP and HR observed when an intruder rat was suddenly introduced into the cage of a resident rat, and confined to the small cage for 15 min. Additionally, the increase in HR and MAP induced by BMA inhibition were eliminated by DMH chemical inhibition. Thus, our data reveal that the BMA is under continuous GABAergic influence, and that its hyperactivation can reduce the physiological response induced by a social novelty condition, possibly by inhibiting DMH neurons

Tobacco-free cigarette smoke exposure induces anxiety and panic-related behaviours in male wistar rats.

Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induced anxiety and panic-related behaviours. Thus, our results contradict the concept that nicotine is solely accountable for shifted behavioural patterns caused by smoking, in that exposure to TFC smoke causes anxiety and panic-related behaviours.Cigarette smoke exposure is associated with anxiety states. Smokers are more anxious than non-smokers1, while cigarette smoking cessation is associated with increased levels of anxiety and stress, as the nicotine in cigarettes has been shown to have anxiolytic effects2. Moreover, smoking is also associated with an augmented risk of panic attacks, and quitting smoking could help reduce this risk3. Importantly, in a study conducted by Amaring and colleagues, it was reported that 72% of panic disorder patients declared that they were regular smokers at the onset of their disease4. Cigarette smoke is also one of the several agents and environmental factors that can trigger oxidative stress and pulmonary damage5. Cigarette smoke causes cellular recruitment, lipid peroxidation, production of inflammatory mediators, and oxidative stress6?11. For instance, studies in mice have shown that exposure to short-term cigarette smoke evokes an increase in inflammatory cell inflow and oxidative damage6,9. In general, exposure to pollutants induces pulmonary inflammation through the generation of oxidative stress12,13, defined as the imbalance in reactive oxygen species production, to the detriment of the antioxidant defence systems14. Importantly, exposure to ambient air particles not only induces pulmonary inflammation but also behavioural disorders both in humans and in mice15. Currently, the majority of anxiety studies associated with cigarette smoking have focused on the anxiolytic effects of nicotine2. However, it has been shown that lung damage can induce central nervous system responses by activating specific neuronal pathways16,17, which include those linked to affective responses, such as anxiety and panic18. This raises the question of whether the anxiety and panic-type behaviour associated with smoking might be related not only to the nicotine or to tobacco?s other constituents but also to lung damage

Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats.

A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ? 16 bpm vs. IVA: 260 ? 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ? 9 bpm vs. IVA: 326 ? 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ? 4.6 vs. IVA: 29.8 ? 6.4; p > 0.05); HF (nu) (VEH: 75.1 ? 3.7 vs. IVA: 69.2 ? 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91? 0.02 vs. IVA: 0.88 ? 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ? 12 bpm vs. IVA: 207 ? 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ? 16 vs. IVA: 120 ? 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ? 4 vs. IVA: 77 ? 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart

Participação do hipotálamo dorsomedial nas respostas cardiovasculares promovidas pela Injeção Intracerebroventricular da tityustoxina escorpiônica em ratos.

Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa e Pós Graduação, Universidade Federal de Ouro Preto.A síndrome do envenenamento escorpiônico é considerada um importante problema de saúde pública, em países tropicais, devido a sua elevada incidência e potencial gravidade dos sintomas, principalmente em crianças. Alguns estudos apontam a grande sensibilidade do sistema nervoso central (SNC) à ação dos componentes tóxicos do veneno e comprovam que as manifestações cardiorespiratórias, consideradas as principais causa mortis do envenenamento, são decorrentes da ativação do sistema nervoso autônomo, sobretudo, da subdivisão simpática. Entretanto, a origem desta modulação permanece desconhecida. Considerando a importante participação do SNC na gênese das repostas hemodinâmicas e cardíacas evocadas pela ação central da Tityustoxina (TsTX, uma α-toxina extraída do veneno do escorpião Tityus serrulatus) e a semelhança destas respostas àquelas mediadas pelo hipotálamo dorsomedial (HDM) em reações de defesa, o objetivo central deste trabalho foi avaliar a participação do HDM nas respostas cardiovasculares decorrentes da injeção i.c.v. de TsTX em ratos. Para tal, em ratos acordados, avaliamos a influência de injeções i.c.v. de diferentes doses de TsTX (1,74μg; 0,174μg; 0,116μg e 0,087μg) sobre os parâmetros cardiovasculares e sobre a porcentagem de letalidade e o tempo de sobrevida. Também realizamos a correlação temporal entre estes parâmetros. Em ratos anestesiados, avaliamos a influência da injeção i.c.v. de TsTX (0,116μg) sobre os parâmetros cardiovasculares e sobre a atividade simpática renal, e o envolvimento dos receptores GABAérgicos e glutamatérgicos ionotrópicos do HDM sobre as alterações cardiovasculares produzidas pela injeção i.c.v. desta dose de TsTX. Dessa forma, nossos principais achados foram: i) a comprovação de uma elevada sensibilidade do SNC à toxicidade exercida pela TsTX; (ii) a relação dose-dependente entre o recrutamento de estruturas encefálicas e o comprometimento cardiovascular (elevação da PAM e FC); (iii) a constatação de uma alta correlação positiva entre a prematuridade das alterações no ritmo cardíaco e a latência para o agravo destas respostas; (iv) uma elevada correlação positiva entre a latência para o agravo das respostas pressora e taquicárdica e o tempo de sobrevida; (v) o aumento da responsividade do nervo simpático renal e (vi) a fundamental participação dos receptores glutamatérgicos ionotrópicos nas respostas hipertensiva e taquicárdica mediadas pela ação central da TsTX. Nossos dados corroboram a hipótese de que o SNC tem uma participação importante na sintomatologia envolvida no envenenamento escorpiônico e sugerem que os circuitos neurais recrutados pela TsTX, cuja ativação resulta em uma variedade de alterações fisiológicas e comportamentais, dependem da ativação dos diferentes subtipos de receptores glutamatérgicos ionotrópicos presentes no HDM.The scorpion envenoming syndrome is an important public health problem, in tropical countries, due to its high incidence and potential severity of symptoms, mainly in children. Some studies address the high sensitivity of the central nervous system (CNS) to the action of the venom toxic components and show that the cardiorespiratory manifestations, which are considered the main causa mortis of scorpion envenoming, are consequences of the autonomic nervous system activation, especially of the sympathetic pathway. However, the origin of this modulation remains unclear. Considering the important CNS participation on the genesis of the cardiovascular responses evoked by the central action of Tityustoxin (TsTX, a α-type toxin extracted from the Tityus serrulatus scorpion venom), and the similarity of these responses, to those mediated by dorsomedial hypotalamus (DMH) in the cardiovascular responses during defense reaction, the central aim of this work was to evaluate the role of DMH on the cardiovascular responses to TsTX i.c.v. injection in rats. To this end, in awake rats, we evaluated the influence of i.c.v. injections of different TsTX doses (1.74μg; 0.174μg; 0.116μg and 0.087μg) on cardiovascular parameters, on lethality percentage and survival time, and a time correlation between these parameters. In anesthetized rats, we evaluated the influence of TsTX i.c.v. injection (0.116μg) on cardiovascular parameters and renal sympathetic nerve activity, and the involvement of GABA and ionotropic glutamate receptors of HDM on cardiovascular alterations induced by i.c.v. injection of this TsTX dose. Thus, our main findings were: i) the evidence of CNS high sensitivity to TsTX toxicity; (ii) the dose-dependent relationship between brain structures recruitment and the cardiovascular compromise (MAP and HR enhance); (iii) a high positive correlation between prematurity of the changes in heart rate and the latency to the grievance of these responses; (iv) a high positive correlation between latency to the grievance of the pressor and tachycardic responses and survival time; (v) the responsiveness increased of renal sympathetic nerve activity and (vi) the essential participation at glutamate receptors in the hypertensive and tachycardic responses mediated by central action of TsTX. Our data support the hypothesis that CNS plays an important role in the symptomathology of scorpion envenomation and suggest that the central circuit recruited by TsTX, whose activation results in an array of physiological and behavioral changes, depend on the activation of the different subtypes of DMH ionotropic glutamate receptors

Efeitos da injeção intracerebroventricular da tityustoxina escorpiônica (tstx) sobre o sistema cardiovascular de ratos submetidos à desnutrição proteica.

A Síndrome do envenenamento escorpiônico constitui um problema de saúde pública mundial, com prevalência alta em países subtropicais, principalmente na faixa etária infantil. A Tityustoxina (TsTX), alvo deste estudo, é uma das principais toxinas extraídas do veneno bruto do T. serrulatus e possui toxicidade elevada. Liga-se ao sítio III dos canais para sódio dependentes de voltagem (CSDVs), retarda o processo de inativação destes canais, aumenta a permeabilidade da membrana ao sódio e, consequentemente, eleva a excitabilidade celular. Há indícios de que as alterações cardiovasculares observadas no envenenamento grave decorrem da ação direta destas toxinas sobre o sistema nervoso central (SNC). Adicionalmente, é sabido que alguns fatores, como a saúde prévia do paciente, podem influenciar na sintomatologia do escorpionismo. Neste contexto, a desnutrição também é uma síndrome de importância epidemiológica mundial que acomete, principalmente, crianças em países em desenvolvimento. Dados prévios do nosso grupo de pesquisa mostraram que ratos desnutridos apresentam alterações nos mecanismos de controle cardiovascular. Assim, a hipótese de que a desnutrição pode ser um fator modificador da ação central da TsTX e de seus efeitos decorrentes torna esse modelo um importante instrumento para o entendimento fisiopatológico do escorpionismo. Esse trabalho objetiva avaliar os efeitos da injeção intracerebroventricular (i.c.v.) de TsTX sobre o Sistema Cardiovascular (SC) de ratos Fischer submetidos à desnutrição protéica. Os ratos (n=69) foram divididos em dois grupos: Normonutrido e Desnutrido, que receberam, respectivamente, 15% e 6% de proteína na dieta. Os animais foram submetidos ao implante de cânulas-guia no Ventrículo Lateral Esquerdo para a microinjeção de TsTX e ao implante de cateteres femorais (venosos e arteriais) e eletrodos, para a infusão de drogas e aquisição dos valores de pressão arterial média (PAM) e de freqüência cardíaca (FC). Os resultados mostraram que a desnutrição protéica reduziu o peso corporal e aumentou os níveis basais de PAM e FC. A microinjeção de TsTX (1,74 μg/μL) induziu o aumento de PAM em ambos os grupos, embora este aumento tenha sido menor e ocorrido com maior latência no grupo Desnutrido. Adicionalmente, elevou a FC apenas no grupo Normonutrido, mas provocou óbito em 100% dos animais dos dois grupos. Contudo, o Grupo Desnutrido apresentou maior sobrevida. O bloqueio dos CSDVs com Carbamazepina (50mg/kg; i.p.) atenuou o aumento de PAM evocado pela TsTX e aumentou a sobrevida apenas dos animais normonutridos. O bloqueio dos receptores α1- adrenégicos com Prazosin reduziu os níveis basais de PAM nos dois grupos, sendo essa redução mais acentuada nos ratos desnutridos. No entanto, aumentou os níveis basais de FC apenas no grupo Normonutrido. Já o bloqueio dos receptores muscarínicos com Metil- atropina não modificou os níveis basais de PAM em nenhum grupo, mas aumentou a FC basal no grupo Normonutrido. Adicionalmente, alterou o perfil das respostas pressora e cronotrópica cardíaca resultantes da ação da TsTX (maior aumento de PAM e elevação da FC), exclusivamente no grupo Desnutrido. Contudo, os bloqueios autonômicos não alteraram a sobrevida dos animais. Finalmente, estes resultados sugerem que a desnutrição atenua a sintomatologia decorrente da ação direta da TsTX sobre o SNC, provavelmente, devido à diminuição dos sítios de ligação (CSDVs) para a toxina. Sendo assim, a gravidade dos sintomas evocados pela injeção i.c.v. de TsTX pode estar estreitamente relacionada à intensidade com que esta toxina age sobre o SNC.The scorpion envenomation syndrome is a public health matter in tropical regions around the world, mainly in children. The Tityustoxin (TsTX), the target of our study, is one of the main toxins extracted from the T. serrulatus scorpion venom. It binds to the site III of the voltage-gated sodium channels (VGSC), slowing its inactivation and increasing the membrane permeability to sodium and cellular excitability. There are evidences that the cardiovascular changes observed in severe scorpion envenomation result from the direct action of these toxins on the central nervous system (CNS). Additionally, it is known that some factors as the patient's previous health may influence scorpion symptoms. In this context, undernutrition is also an important global epidemiological syndrome that mainly affects children in developing countries. Previous data from our laboratory have shown that undernourished rats present changes in cardiovascular control mechanisms. Thus, we hypothesized that undernutrition may be a modifying factor for the TsTX central action and its effects makes the undernutrition model an important tool to understand the scorpion envenomation. The objective of this work was to assess the effects of TsTX injection in left lateral ventricle (LLV) on the Cardiovascular System (CS) of Fischer rats submitted to protein restriction diet. Rats (n=69) were divided into two groups: Wellnourished and Undernourished groups, which received, respectively, 15% and 6% of protein in the diet composition. Animals were submitted to guide cannulae implantation into the LLV for TsTX microinjection, femoral catheters (arterial and venous) and electrodes implantation for drugs infusion and mean arterial pressure (MAP) and heart rate values acquisition (HR). Our results showed that the undernutrition model reduced the body weight and increased the MAP and HR baseline values. The TsTX microinjection (1.74 µg/µL) induced a MAP increase in both groups, although this increase was smaller and occurred with higher latency in the Undernourished group. Moreover, the TsTX induced a HR elevation only in the Wellnourished group. It induced death in 100% of the animals from both groups. Nevertheless, the Undernourished group had a greater survival time. The VGSC blockade with Carbamazepine (50mg/kg, i.p.) attenuated the MAP increase evoked by TsTX microinjection and increased the survival time only in Wellnourished group. The α1- adrenergic receptors blockade with Prazosin (1mg/kg/mL; i.v.) reduced MAP basal levels in both groups, mainly in the Undernourished rats. However, there was an increase in HR basal levels only in Wellnourished group. On the other hand, the muscarinicreceptors blockade with methyl-atropine (1mg/kg/mL; i.v.) did not affect MAP basal levels in both groups, although there was an increase in HR only in the Wellnourished group. Additionally, it changes the pressor and chronotropic cardiac responses profile resulting from the TsTX action (higher increase in MAP and HR elevation), exclusively in Undernourished group. Besides, the blockade with both drugs did not modify the survival rate in neither group. Finally, these results suggest that the protein restriction attenuates the manifestations resulting from TsTX action on CNS, probably due to a reduction in biding sites (VGSCs) for TsTX. Thus, the severity of symptoms evoked by TsTX injection in LLV may be closely related with the intensity which this toxin acts on CNS

Biomarcadores hep?ticos de inflamaci?n y su v?nculo con la obesidad y las enfermedades cr?nicas.

Introduction: The low-grade inflammation and insulin resistance are two events that could be present in varying degrees, on obesity and chronic diseases. The degree of subclinical inflammation can be gauged by measuring the concentrations of some inflammatory biomarkers, including the hepatic origin ones. Some of those biomarkers are sialic acid, ?1-antitrypsin and the C-terminal fragment of alpha1-antitrypsin, ceruloplasmin, fibrinogen, haptoglobin, homocystein and plasminogen activator inhibitor-1. Objectives: To approach the relation between adiposity and hepatic inflammatory markers, and to assess the possible associations between hepatic inflammatory biomarkers and obesity, as well as their capacity of predicting chronic diseases such as type 2 diabetes and atherotrombotic cardiovascular diseases. Methods: We used electronic scientific databases to select articles without restricting publication year. Results: The sialic acid predicts the chance increase to become type2 diabetic independently of BMI. Moreover, the ?1-antitripsin, ceruloplasmin, fibrinogen and haptoglobulin biomarkers, seem predict the chance increase to become type2 diabetic, dependently, of BMI. So, this process could be aggravated by obesity. The concentrations of fibrinogen, homocystein and PAI-1 increase proportionally to insulin resistance, showing its relation with metabolic syndrome (insulin resistance state) and with type2 diabetes. In relation to cardiovascular diseases, every biomarkers reported in this review seem to increase the risk, becoming useful in add important prognostic. Conclusion: This review integrates the knowledge concerning the possible interactions of inflammatory mediators, in isolation or in conjunction, with obesity and chronic diseases, since these biomarkers play different functions and follow diverse biochemical routes in human body metabolism.RESUMEN: Introduci?n: El bajo grado de inflamaci?n y la resist?ncia a la insulina son dos eventos que podr?an estar presentes en mayor o menor grado, en la obesidad y las enfermedades cr?nicas. El grado de inflamaci?n subcl?nica se puede evaluar por medici?n de las concentraciones de algunos biomarcadores inflamatorios, incluyendo los de origen hep?tico. Algunos de estos biomarcadores son El ?cido si?lico, ?1-antitripsina y el fragmento C-terminal de la alfa 1-antitripsina, ceruloplasmina, fibrin?geno, haptoglobina, la homociste?na y el inhibidor-1 del activador del plasmin?geno. Objetivos: Evaluar la relaci?n entre la obesidad y l?s marcadores de inflamaci?n hep?tica, y las posibles asociaciones entre los biomarcadores inflamatorios hep?ticos y la obesidad, as? como su capacidad de predicci?n de las enfermedades cr?nicas como la diabetes tipo 2 y enfermedades cardiovasculares aterotromboticas. M?todos: Se utilizaron bases cient?ficas electr?nicas para selecci?n de art?culos, sin l?mite de a?o de publicaci?n. Resultados: El ?cido si?lico predice el aumento de convertirse en diab?ticos tipo 2 independientemente Del IMC. Por otra parte, los biomarcadores ?1-antitripsina, ceruloplasmina, fibrin?geno y haptoglobulina, parecen predecir el aumento de convertirse en diab?tico tipo 2, dependiente, de IMC. Por lo tanto, este proceso podr?a verse agravada por la obesidad. Las concentraciones de fibrin?geno, homociste?na y PAI-1 incrementam proporcionalmente a la insulinoresist?ncia, mostrando su relaci?n con el s?ndrome metab?lico (estado de resist?ncia insul?nica) y con la diabetes tipo 2. En relaci?n con l?s enfermedades cardiovasculares, cada biomarcador informado en esta revisi?n parece aumentar el riesgo, llegando a ser muy ?til en el complemento pron?stico. Conclusion: Esta revisi?n se integra el conocimiento acerca de las posibles interacciones de los mediadores inflamatorios, en forma aislada o en combinaci?n, con La obesidad y las enfermedades cr?nicas, ya que estos biomarcadores desempe?an funciones diferentes y siguen diversas rutas bioqu?micas en el metabolismo del cuerpo humano

Prospects about the use of Açaí (Euterpe oleracea Mart.) on the Modulation of the Inflammation and energetic metabolism in overweight and obese individuals.

The adiposity excess has as consequences metabolic complications which could predispose to the onset of chronic diseases concomitantly to induction of an inflammatory condition of low intensity by means of the secretion and expression of inflammatory cytokines in adipose tissue. These cytokines (IL-2, IL-4, IL-13, IL-15 e IFN-γ) may be involved in the regulation of energetic metabolism and food intake, contributing or minimizing the adipose tissue expansion. Some factors modulate the inflammation, such as body composition, biochemical, clinical and dietary parameters. The high intake of polyphenols, which is essential to preserve the metabolic homeostasis and control the subclinical inflammation, has been correlated to low incidence of chronical diseases. The açaí is a fruit rich in polyphenols which has been investigated due to its antioxidant and antiinflammatory effects. However, so far, its effects are not clear in humans. The perspective is that the açaí pulp intake could play beneficial effect on the inflammatory, anthropometric, metabolic and body composition states on the obesity process

What is the role of inflammatory mediators on energy metabolism?

The subclinical and low intensity inflammation, oxidative stress, high calorie and high fat diet patterns are striking features of the obesity. The adipose tissue, through its endocrine function, is associated with the cytokines secretion, such as: IL-4, IL-13, IL-15 and IFN-?, which trigger metabolic changes and possibly modulate the energy metabolism by modifying the biochemical, anthropometric and body composition parameters. This review summarizes scientific evidences about the relationship between such cytokines and mediators which alter the energy metabolism, predisposing or preventing the obesity

The implication of protein malnutrition on cardiovascular control systems in rats.

The malnutrition in early life is associated with metabolic changes and cardiovascular impairment in adult hood. Deficient protein intake-mediated hypertension has been observed in clinical and experimental studies. In rats, protein malnutrition also increases the blood pressure and enhances heart rate and sympathetic activity. In this review, we discuss the effects of post-weaning protein malnutrition on the resting mean arterial pressure and heartrate and their variabilities, cardiovascular reflexes sensitivity, cardiac autonomic balance, sympathetic and renin-angiotensin activities and neural plasticity during adult life. These insights reveal an interesting prospect on the autonomic modulation underlying the cardiovascular imbalance and provide relevant information preventing cardiovascular diseases

Nitric oxide modulates blood pressure through NMDA receptors in the rostral ventrolateral medulla of conscious rats.

The rostral ventrolateral medulla (RVLM) is an important site of cardiovascular control related to the tonic excitation and regulating the sympathetic vasomotor tone through local presympathetic neurons. Nitric oxide (NO) has been implicated in the modulation of neurotransmission by several areas of the central nervous system including the RVLM. However the path ways driving NO affects and the correlation between NO and glutamate-induced mechanisms are not well established. Here, we investigate the influence of NO on the cardiovascular response evoked by the activation of NMDA and non-NMDA glutamatergic receptors in the RVL Minconscious rats. For that, we examined the influence of acute inhibition of the NO production with in the RVLM, by injecting the nonselective constitutive NOS inhibitor, L-NAME, on responses evoked by the microinjection of excitatory aminoacids L-glutamate, NMDA or AMPA agonists into RVLM. Our results show that the injection of L-glutamate, NMDA or AMPA agonists in to RVLM, unilaterally, induced a marked increase in the mean arterial pressure (MAP). Pretreament with L-NAME reduced the hypertensive response evoked by the glutamate injection, and also abolished the pressor response induced by the injection of NMDA in to the RVLM. However, block ng the NO synthesis did not alter the response produced by the injection of AMPA agonist. These data provide evidence that the glutamatergic neuro transmission with in the RVLM depend son excitatory effects exerted by NO on NMDA receptors, and that this mechanism might be essential to regulate systemic blood pressure