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AIMS: This study aimed to evaluate the short- and long-term adverse effects of blood pressure (BP), vascular endothelial function, and estrogen receptor (ERα and ERß) modulation on endothelial function in female Wistar rats treated with topiramate (TPM), an antiepileptic drug, during the peripubertal period. MATERIALS AND METHODS: Female Wistar rats were treated with TPM (41 mg/kg) or water (CTR group) by gavage from postnatal day (PND) 28 to 50 (peripubertal phase). At the end of the treatment, the TPM and CTR rats were divided into two groups and evaluated after 24 h or from PND 85 (adulthood). The rats were evaluated for: thoracic aorta reactivity to phenylephrine (Phenyl), acetylcholine (ACh), and sodium nitroprusside (SNP); aortic ring reactivity after ERα and ERß antagonism; and BP. KEY FINDINGS: It was observed that vascular response to Phenyl, ACh, and SNP was similar between TPM and CTR rats in the short- and long-term evaluations. In addition, the ER antagonism did not interfere with aortic contraction or relaxation in either TPM or CTR. SIGNIFICANCE: Taken together, the results show that TPM treatment during the peripubertal period does not alter aortic endothelial function and its estrogen modulation via classic ER in female Wistar rats, suggesting that TPM treatment in this period is safe for the vascular system.
Assuntos
Receptor alfa de Estrogênio , Receptor beta de Estrogênio , Ratos , Feminino , Animais , Ratos Wistar , Topiramato/farmacologia , Vasoconstrição , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Receptores de Estrogênio , Acetilcolina/farmacologia , Endotélio VascularRESUMO
Considering depression is three times more common in cardiac patients compared to the normal population and selective serotonin reuptake inhibitors (SSRI) as drug of choice for treating patients with cardiovascular disease and depression, our work aims to evaluate the cardiovascular effects of treatment for 21 days with escitalopram (5â¯mg/kg/day, ip) in rats. The treatment caused an increase in mean arterial pressure concomitant with a decrease in heart rate. Concerning heart rate variability, there was a significant reduction in the sympathetic component and an elevation of the parasympathetic component, indicating that escitalopram caused an autonomic imbalance with parasympathetic predominance. In addition, we observed a decrease in both low and very low frequency power in blood pressure variability. The cardiac autonomic blockade indicated an increase in parasympathetic modulation to the heart with escitalopram chronic treatment. However, no change was observed on baroreflex activity. On the other hand, there was a decrease in pressure response during acute restraint stress with no changes in the tachycardia response. These findings showed that despite the escitalopram be a relatively safe drug it can cause tonic effects on cardiovascular function as well as during aversive situations.
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Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Citalopram/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiologia , Barorreflexo/efeitos dos fármacos , Sistema Cardiovascular/inervação , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/fisiopatologiaRESUMO
The use of light emitting diodes (LED) as a therapeutic resource for wound healing has increased over the last years; however, little is still known about the molecular pathways associated to LED exposure. In the present study, we verified the effects of LED therapy on DNA methylation and expression of the DNA methyltransferase (Dnmt) genes, Dnmt1 and Dnmt3a, in an in vivo model of epithelial wound healing. Male Wistar rats were submitted to epithelial excision in the dorsal region and subsequently distributed within the experimental groups: group 1, animals that received irradiation of 0.8 J/cm(2) of LED (604 nm); group 2, animals that received 1.6 J/cm(2) of LED (604 nm); control (CTL), animals not submitted to therapeutic intervention. LED applications were performed during 7 days, and tissues from the periphery of the wound area were obtained for molecular analysis. The Image-J software was used for analysis of the wound area. DNA methylation was evaluated by ELISA-based method and gene expressions were quantified by real-time PCR. Decrease on global DNA methylation profile was observed in all experimental groups (CTL, 1, and 2) revealing the participation of DNA methylation in the healing process. Significant decrease in the wound area accompanied by increase in the Dnmt3a expression was associated to group 2. Based on our findings, we propose that DNA methylation is an important molecular mechanism associated to wound healing and that irradiation with 1.6 J/cm(2) of LED evokes an increase in the expression of the Dnmt3a that might associates to the efficiency of the epithelial wound healing.
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DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos da radiação , Regulação Enzimológica da Expressão Gênica/efeitos da radiação , Terapia a Laser , Pele/patologia , Cicatrização/genética , Cicatrização/efeitos da radiação , Animais , DNA (Citosina-5-)-Metiltransferase 1 , DNA Metiltransferase 3A , Modelos Animais de Doenças , Masculino , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Pele/efeitos da radiaçãoRESUMO
Depression is one of the most prevalent disorders in the world and may occur during pregnancy and postpartum periods. Fluoxetine (FLX) has been widely prescribed for use during depression in pregnancy and lactation. This study aimed to investigate if in utero and lactational exposure to FLX could compromise reproductive parameters in female offspring. Wistar rats received, by daily gavage, FLX 5mg/kg or 0.3ml of water (control group) from the first gestational day until weaning (21 days). Assessments in the female offspring included: body weight, anogenital distance, vaginal opening, first estrus, estrous cycle, reproductive organs weight, uterine morphometric analyses, ovarian follicle and corpora lutea counting, estradiol plasmatic concentration, sexual behavior, maternal behavior and fertility test. Exposure to FLX delayed the puberty onset in female pups. The present study demonstrated that developmental exposure to FLX can deregulate the neuroendocrine hormonal control of female offspring during prepubertal and pubertal periods.
Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Fluoxetina/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Maturidade Sexual/efeitos dos fármacos , Animais , Estradiol/sangue , Ciclo Estral/efeitos dos fármacos , Feminino , Fertilidade/efeitos dos fármacos , Lactação , Masculino , Comportamento Materno/efeitos dos fármacos , Troca Materno-Fetal , Ovário/anatomia & histologia , Ovário/efeitos dos fármacos , Gravidez , Ratos Wistar , Comportamento Sexual Animal/efeitos dos fármacos , Útero/anatomia & histologia , Útero/efeitos dos fármacosRESUMO
AIMS: The dorsal periaqueductal gray matter (dPAG) is involved in the integration of behavioral and cardiovascular responses caused by fear and anxiety situations. Some studies suggest an involvement of noradrenergic neurotransmission in the dPAG in anxiety modulation, however, there is no evidence about its role in panic attacks. The goal of this work was to study the effect of NA microinjection in dPAG in rats submitted to the elevated T-maze (ETM). MATERIALS AND METHODS: Male Wistar had a cannula implanted in the PAG where it was injected NA in the doses of 1, 3, 15, 45nmol/50nl or artificial cerebrospinal fluid previous the ETM test. KEY FINDINGS: NA intra-dPAG decreased inhibitory avoidance behavior in the ETM without changing escape, indicating only an anxiolytic-like effect. Furthermore, the microinjection of NA did not change the general exploratory activity of the animals submitted to the open field test, suggesting that the anxiolytic-like effect is not due to an increase in exploratory activity. SIGNIFICANCE: The results indicate an involvement of noradrenergic neurotransmission in the dPAG in defensive reactions associated with generalized anxiety, but not as main mechanisms for the panic, in rats submitted to the elevated T-maze providing support for other research aimed at improving the treatment of generalized anxiety.
Assuntos
Ansiolíticos/farmacologia , Norepinefrina/farmacologia , Substância Cinzenta Periaquedutal , Simpatomiméticos/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/psicologia , Relação Dose-Resposta a Droga , Reação de Fuga/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Masculino , Microinjeções , Norepinefrina/administração & dosagem , Ratos , Ratos Wistar , Simpatomiméticos/administração & dosagem , Transmissão Sináptica/efeitos dos fármacosRESUMO
Resumo:OBJETIVO:avaliar a influência do tratamento com fármacos antivertiginosos sobre a qualidade de vida e o equilíbrio postural de adultos e idosos com queixas de tontura.MÉTODOS:estudo transversal, com amostra de 51 indivíduos portadores de queixas de tontura, divididos em dois grupos, de acordo com o uso (grupo medicado, n=25) ou não (grupo não medicado, n=26) de fármacos antivertiginosos. Foram coletadas informações sobre: caracterização dos sintomas (ficha elaborada pelos pesquisadores), autopercepção de qualidade de vida (Dizziness Handicap Inventory),intensidade de tontura (escala visual analógica de tontura) e equilíbrio postural (plataforma de força).RESULTADOS:verificou-se intensidade moderada de tontura (Média: 4,6 ± 2,8) e impacto negativo das vestibulopatias sobre a qualidade de vida (Média: 47,3 ± 22,4) na amostra total. Quando comparados os dois grupos, não houve diferença estatisticamente significante na intensidade da tontura (p=0,74) ou qualidade de vida (p=0,79), e também, nos parâmetros da estabilometria, em quatro tarefas (teste t independente, p>0,05). Contudo, após a inclusão do tempo de utilização de fármacos antivertiginosos como uma covariável do estudo, foi verificado pior desempenho nas diferentes tarefas da estabilometria no grupo medicado (ANCOVA, p<0,05).CONCLUSÃO:o uso de fármacos antivertiginosos não melhora a qualidade de vida de indivíduos com queixas de tontura e o equilíbrio postural esteve alterado no grupo medicado.
Abstract:PURPOSE:this study aimed to identify the influence of anti-vertigo drugs on the health-related quality of life and balance in adults and elder individuals with dizziness complaints.METHODS:51 individuals with dizziness complaints were enrolled at this cross-sectional study. The sample was divided into two groups according to chronic use of antivertigo drugs (medicated group, n=25 or non-medicated group, n=26). Information regarding vertigo-related symptoms, health-related quality of life (through Dizziness Handicap Inventory), dizziness intensity (measured by dizziness visual analogue scale) and postural balance (using a force platform) were assessed in all subjects recruited.RESULTS:a moderate intensity of dizziness was observed (Mean: 4.6 ± 2.8) as well as negative impact on health-related quality of life (Mean: 47.3 ± 22.4) at this sample. When medicated and non-medicated groups were compared, no statistically differences were observed concerning dizziness intensity (p=0.74) and health-related quality of life (p=0.79). Similar results were observed regarding balance parameters (Unpaired t test, p > 0.05). However, after including the time duration of antivertigo drugs' use as a covariable of this study, a worse balance in different balance tasks was observed at the medicated group (ANCOVA, p<0.05).CONCLUSION:no benefits concerning the symptoms or health-related quality of life were observed after chronic treatment with anti-vertigo drugs. On the other hand, worse balance control was observed in medicated group.
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Introduction Dizziness can be characterized as a balance disorder that causes discomfort, leading to several functional limitations. Currently, vestibular rehabilitation has been highlighted as a possible treatment. Objective Analyze the effects of completing a vestibular rehabilitation treatment protocol on quality of life and postural balance in patients with vestibular complaints, as well as to compare these effects between the patients taking or not taking antivertigo drugs. Methods A nonrandomized controlled trial was performed with 20 patients previously diagnosed with vestibular diseases. Information regarding vertigo symptoms, quality of life as assessed through the Dizziness Handicap Inventory, visual analog scale of dizziness, and stabilometry using force platform was collected. Patients were treated for 12 weeks by a customprotocol. The sample was divided into two groups according to the use (medicated group, n = 9) or not (control group, n = 11) of antivertigo drugs. Results There was improvement in quality of life (p < 0.001) and intensity of dizziness (p = 0.003) with the intervention. An improvement of postural balance was observed through functional tests. However, no statistically significant difference was noted in stabilometry. When both groups were compared, no statistically significant differences between the variations of the variables analyzed were found in the re-evaluation session. Conclusion Quality of life and postural balance are improved with intervention. However, this improvement is not associated with pharmacologic treatment.
Assuntos
Masculino , Feminino , Adulto , Idoso , Fármacos do Sistema Nervoso Central , Equilíbrio Postural , Postura , Qualidade de Vida , Sinais e Sintomas , Vertigem/reabilitação , Brasil , Guias como AssuntoRESUMO
Introduction Dizziness can be characterized as a balance disorder that causes discomfort, leading to several functional limitations. Currently, vestibular rehabilitation has been highlighted as a possible treatment. Objective Analyze the effects of completing a vestibular rehabilitation treatment protocol on quality of life and postural balance in patients with vestibular complaints, as well as to compare these effects between the patients taking or not taking antivertigo drugs. Methods A nonrandomized controlled trial was performed with 20 patients previously diagnosed with vestibular diseases. Information regarding vertigo symptoms, quality of life as assessed through the Dizziness Handicap Inventory, visual analog scale of dizziness, and stabilometry using force platform was collected. Patients were treated for 12 weeks by a custom protocol. The sample was divided into two groups according to the use (medicated group, n = 9) or not (control group, n = 11) of antivertigo drugs. Results There was improvement in quality of life (p < 0.001) and intensity of dizziness (p = 0.003) with the intervention. An improvement of postural balance was observed through functional tests. However, no statistically significant difference was noted in stabilometry. When both groups were compared, no statistically significant differences between the variations of the variables analyzed were found in the re-evaluation session. Conclusion Quality of life and postural balance are improved with intervention. However, this improvement is not associated with pharmacologic treatment.
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The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular modulation. In a previous study, we showed that noradrenaline (NA) microinjected into the dPAG caused a vasopressin-mediated pressor response, involving a relay in the hypothalamic paraventricular nucleus (PVN). In the present study, we evaluated the involvement of ionotropic glutamate receptors within the PVN in the cardiovascular response to NA microinjection into the dPAG of unanesthetized rats. Microinjection of the selective NMDA glutamate receptor antagonist LY235959 (2nmol/100nL) unilaterally into the PVN did not affect the cardiovascular response evoked by microinjection of NA (15nmol/50nL) into the dPAG. On the other hand, unilateral PVN pretreatment with the non-NMDA glutamate receptor antagonist NBQX (2nmol/100nL) significantly reduced the pressor and cardiac response caused by microinjection of NA into the dPAG. In addition, bilateral PVN pretreatment with NBQX (2nmol/100nL) blocked the cardiovascular response to NA injected into the dPAG. In conclusion, the present results suggest that bilateral PVN activation of non-NMDA glutamate receptors mediates the vasopressin-related cardiovascular response to the microinjection of NA into the dPAG.
Assuntos
Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Norepinefrina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Agonistas alfa-Adrenérgicos/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicardia/metabolismo , Cateteres de Demora , Antagonistas de Aminoácidos Excitatórios/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Isoquinolinas/farmacologia , Masculino , Microinjeções , Norepinefrina/administração & dosagem , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Quinoxalinas/farmacologia , Ratos Wistar , Receptores de AMPA/antagonistas & inibidores , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
A growing body of evidence has drawn the attention of the scientific community by indicating the potential vulnerability to environmental changes of epigenetic mechanisms that control gene expression. Being critical components of normal development, the importance of epigenetic mechanisms for normal biology is illustrated by the fact that abnormal epigenetic patterns have increasingly been linked to the aetiology of various diseases including cancer, paediatric syndromes, autoimmune diseases, genetic disorders and even the molecular process of ageing. It is estimated that the degree of vulnerability to changes in epigenetic patterns is high during early embryonic development, a period of life in which epigenetic patterns are established and cell differentiation is intense. Moreover, increasing amounts of relevant data and information reveal that the environment might potentially impact on epigenetic patterns at every period of life. Within this context, in this study we will review the principles of epigenetic vulnerability to environmental changes, the impacts on development, the association with the origin of common diseases and also speculate about the potential of lifestyle changes to modulate epigenetic patterns and contribute to preventing common diseases.
Assuntos
Saúde Ambiental , Epigênese Genética/genética , Epigênese Genética/fisiologia , Envelhecimento/genética , Envelhecimento/fisiologia , Metilação de DNA/genética , Metilação de DNA/fisiologia , Feminino , Humanos , Estilo de Vida , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologiaRESUMO
Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.
Assuntos
Envelhecimento , Fluoxetina/farmacologia , Lactação/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Caracteres Sexuais , Tonsila do Cerebelo/metabolismo , Animais , Feminino , Masculino , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Estresse Psicológico/etiologia , Estresse Psicológico/metabolismoRESUMO
The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Glutamate (L-Glu) is an abundant excitatory amino acid in the central nervous system (CNS) and is present in the rat PAG. Moreover, data in the literature indicate its involvement in central blood pressure control. Here we report on the cardiovascular effects caused by microinjection of L-Glu into the dorsomedial PAG (dmPAG) of rats and the glutamatergic receptors as well as the peripheral mechanism involved in their mediation. The microinjection of L-Glu into the dmPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. The cardiovascular response was significantly reduced by pretreatment of the dmPAG with a glutamatergic M-methyl-D-aspartate (NMDA) receptor antagonist (LY235959) and was not affected by pretreatment with a non-NMDA receptor antagonist (NBQX), suggesting a mediation of that response by the activation of NMDA receptors. Furthermore, the pressor response was blocked by pretreatment with the ganglion blocker pentolinium (5 mg/kg, intravenously), suggesting an involvement of the sympathetic nervous system in this response. Our results indicate that the microinjection of L-Glu into the dmPAG causes sympathetic-mediated pressor responses in unanesthetized rats, which are mediated by glutamatergic NMDA receptors in the dmPAG.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Masculino , Microinjeções , Ratos , Ratos WistarRESUMO
In the present study, we describe the cardiovascular effects of local acetylcholine (Ach) microinjection into both the ventrolateral (vlPAG) and dorsal (dPAG) periaqueductal gray areas of anesthetized rats and the possible local receptors involved with these responses. Microinjection of Ach (9, 27, 45 or 81 nmol/50 nL) into the vlPAG caused dose-related depressor responses. These hypotensive responses were blocked by local pretreatment with increasing doses of the nonselective muscarinic antagonist atropine (1, 3 or 9 nmol/50 nL)(.) The microinjection of Ach into the dPAG caused no significant cardiovascular responses in anesthetized rats. In conclusion, the present findings suggest that a cholinergic system present in the vlPAG, but not in the dPAG, is involved with cardiovascular system control. Moreover, these cardiovascular responses evoked by Ach are mediated by muscarinic receptors.
Assuntos
Acetilcolina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Acetilcolina/toxicidade , Animais , Atropina/farmacologia , Fibras Colinérgicas/ultraestrutura , Hipotensão/induzido quimicamente , Masculino , Microinjeções , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos WistarRESUMO
AIMS: The dorsal periaqueductal gray area (dPAG) is involved in cardiovascular modulation. Previously, we reported that noradrenaline (NA) microinjection into the dPAG caused a pressor response that was mediated by vasopressin release into the circulation. However, the neuronal pathway that mediates this response is as yet unknown. There is evidence that chemical stimulation of the diagonal band of Broca (dbB) also causes a pressor response mediated by systemic vasopressin release. In the present study, we evaluated the participation of the dbB in the pressor response caused by NA microinjection into the dPAG as well as the existence of neural connections between these areas. MAIN METHODS: With the above goal, we verified the effect of the pharmacological ablation of the dbB on the cardiovascular response to NA microinjection into the dPAG of unanesthetized rats. In addition, we microinjected the neuronal tracer biotinylated-dextran-amine (BDA) into the dPAG and looked for efferent projections from the dPAG to the dbB. KEY FINDINGS: The pharmacologically reversible ablation of the dbB with local microinjection of CoCl(2) significantly reduced the pressor response caused by NA microinjection (15 nmol/50 nL) into the dPAG. In addition, BDA microinjection into the dPAG labeled axons in the dbB, pointing to the existence of direct connections between these areas. SIGNIFICANCE: The present results indicate that synapses within the dbB are involved in the pressor pathway activated by NA microinjection into the dPAG and direct neural projection from the dPAG to the dbB may constitute the neuroanatomic substrate for this pressor pathway.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Feixe Diagonal de Broca/efeitos dos fármacos , Norepinefrina/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais , Biotina/análogos & derivados , Biotina/farmacologia , Pressão Sanguínea/fisiologia , Mapeamento Encefálico , Cobalto/farmacologia , Dextranos/farmacologia , Feixe Diagonal de Broca/fisiologia , Vias Eferentes/efeitos dos fármacos , Vias Eferentes/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Microinjeções , Norepinefrina/administração & dosagem , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Wistar , Sinapses/efeitos dos fármacos , Sinapses/fisiologiaRESUMO
The paraventricular nucleus of the hypothalamus (PVN) has been implicated in several aspects of cardiovascular control. Stimulation of the PVN evokes changes in blood pressure and heart rate. Additionally, this brain area is connected to several limbic structures implicated in behavioral control, as well as to forebrain and brainstem structures involved in cardiovascular control. This evidence indicates that the PVN may modulate cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint is an unavoidable stressor that evokes marked and sustained cardiovascular changes, which are characterized by elevated mean arterial pressure (MAP) and an intense heart rate (HR) increase. We report on the effect of inhibition of PVN synapses on MAP and HR responses evoked by acute restraint in rats. Bilateral microinjection of the nonspecific synaptic blocker cobalt (CoCl(2), 1 mM/100 nl) into the PVN did not change the HR response or the initial peak of the MAP response to restraint stress, but reduced the area under the curve of the MAP response. Moreover, bilateral microinjection of cobalt in areas surrounding the PVN did not change the cardiovascular response to restraint. These results indicate that synapses in the PVN are involved in the neural pathway that controls blood pressure changes evoked by restraint.
Assuntos
Sistema Cardiovascular/fisiopatologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Área Sob a Curva , Pressão Sanguínea/fisiologia , Cobalto/farmacologia , Frequência Cardíaca/fisiologia , Masculino , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ratos , Ratos Wistar , Restrição Física , Estresse Fisiológico , Sinapses/efeitos dos fármacos , Sinapses/fisiologiaRESUMO
Microinjection of l-glutamate (l-glu: 1, 3, 10 and 30nmol/100nL) into the lateral hypothalamus (LH) caused dose-related depressor and bradycardiac responses. The cardiovascular response to l-glu stimulation of the LH was blocked by pretreatment of the ventrolateral portion of the periaqueductal gray matter (vlPAG) with CoCl2 (1mM/100nL), indicating the existence of a synaptic relay of the hypotensive pathway in that area. Furthermore, the response to l-glu was blocked by pretreatment of the vlPAG with 2nmol/100nL of the selective NMDA-receptor antagonist LY235959 and was not affected by pretreatment with 2nmol/100nL of the selective non-NMDA-receptor antagonist NBQX, suggesting a mediation of the hypotensive response by NMDA receptors in the vlPAG. In conclusion, our results indicate that the hypotensive pathway activated by microinjection of l-glu into the LH involves a NMDA synaptic relay in the vlPAG.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Região Hipotalâmica Lateral/efeitos dos fármacos , Substância Cinzenta Periaquedutal/fisiologia , Anestesia , Animais , Cobalto/farmacologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Isoquinolinas/farmacologia , Masculino , Microinjeções/métodos , Bloqueio Nervoso/instrumentação , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Quinoxalinas/farmacologia , Ratos , Ratos WistarRESUMO
The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Noradrenaline (NA), a neurotransmitter involved in central blood pressure control, is present in the rat PAG. We report here on the cardiovascular effects caused by NA microinjection into the ventrolateral PAG (vlPAG) of unanesthetized rats and the peripheral mechanism involved in their mediation. NA microinjection in the vlPAG of unanesthetized rats evoked dose-related pressor and bradycardiac responses. No significant cardiovascular responses were observed in urethane-anesthetized rats. The pressor response was potentiated by pretreatment with the ganglion blocker pentolinium (5 or 10 mg/kg, intravenously). Pretreatment with the vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 microg/kg, intravenously) blocked the pressor response evoked by the NA microinjection into the vlPAG. Additionally, circulating vasopressin content was found to be significantly increased after NA microinjection in the vlPAG. The results suggest that activation of noradrenergic synapses within the vlPAG modulates vasopressin release in unanesthetized rats.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Norepinefrina/administração & dosagem , Substância Cinzenta Periaquedutal , Vasoconstritores/administração & dosagem , Anestésicos Intravenosos , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Bloqueadores Ganglionares/administração & dosagem , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/farmacologia , Injeções Intravenosas , Masculino , Microinjeções , Norepinefrina/antagonistas & inibidores , Norepinefrina/farmacologia , Tartarato de Pentolínio/administração & dosagem , Tartarato de Pentolínio/farmacologia , Ratos , Ratos Wistar , Uretana , Vasoconstritores/antagonistas & inibidores , Vasoconstritores/farmacologia , Vasopressinas/antagonistas & inibidores , Vasopressinas/sangueRESUMO
The medial prefrontal cortex (MPFC) is a structure that is also involved in cardiovascular modulation. The injection of norepinephrine (NE) into the prelimbic (PL) area of the MPFC of unanesthetized rats evokes a pressor response which is mediated by acute vasopressin release. Vasopressin is synthesized by magnocellular cells of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. In the present study, we endeavored to determine which vasopressin-synthesizing hypothalamic nucleus is involved in the pressor pathway activated after NE injection into the PL area of the MPFC. We report here that lidocaine microinjection into the SON did not change the pressor response evoked by NE injection into the PL. However, the response to NE was blocked by prior injection of lidocaine or CoCl(2) into the PVN, indicating that this area is responsible for the mediation of this pressor response. A neuroanatomic experiment in which the neuronal tracer biotinylated dextran amine (BDA) was microinjected into the MPFC showed a lack of axons or neuronal cell bodies in the PVN, indicating that there are no direct connections between the PL area of the MPFC and the PVN. The results suggest that the PVN is involved in the mediation of the pressor response to NE in the PL area and that this pathway must relay in other brain structures before reaching the PVN.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Norepinefrina/farmacologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Simpatomiméticos/farmacologia , Vigília , Anestésicos Locais/farmacologia , Animais , Antimutagênicos/farmacologia , Pressão Sanguínea/fisiologia , Cobalto/farmacologia , Interações Medicamentosas , Lidocaína/farmacologia , Masculino , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Wistar , Vasopressinas/metabolismoRESUMO
Injection of noradrenaline (NA) into the lateral cerebral ventricle (i.c.v.) was reported to cause blood pressure increase in unanesthetized rats, blocked by i.v. injection of vasopressin antagonists. We report similar responses to NA injection into the III or IV ventricles, suggesting multiple sites of action for i.c.v. NA. These responses were blocked by i.v. pretreatment with vasopressin antagonist, suggesting a common mediation by vasopressin release into circulation. Selected ventricular spaces were occluded with Nivea cream plugs to identify ventricular areas responding to i.c.v. NA. III ventricle or aqueduct occlusions markedly reduced pressor responses to i.c.v. NA. Microinjection of NA into the periaqueductal gray matter (PAG) caused pressor responses that were similar to those of i.c.v. NA, reinforcing the idea of a site of action in the aqueduct. IV ventricle occlusion only partially blocked the response to i.c.v. NA. The results suggest at least two sites of action for i.c.v. NA in unanesthetized rats. A primary site located in the PAG and another on the IV ventricle wall.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Norepinefrina/farmacologia , Vasoconstritores/farmacologia , Animais , Aqueduto do Mesencéfalo , Ventrículos Cerebrais/anatomia & histologia , Injeções Intraventriculares , Masculino , Microinjeções , Norepinefrina/administração & dosagem , Substância Cinzenta Periaquedutal , Ratos , Ratos Wistar , Rombencéfalo , Vasoconstritores/administração & dosagem , Vasopressinas/antagonistas & inibidoresRESUMO
The periaqueductal grey area (PAG) is a mesencephalic region that is involved in the modulation of cardiovascular changes associated with behavioural responses. Among the neurotransmitters present in the PAG, noradrenaline (NA) is also known to be involved in central nervous system cardiovascular regulation. In the present study we report the cardiovascular effects of the microinjection of NA into the dorsal portion of the PAG (dPAG) of unanaesthetized rats and the peripheral mechanism involved in their mediation. Injection of NA in the dPAG of unanaesthetized rats evoked a dose-dependent pressor response accompanied by bradycardia. The magnitude of the pressor responses was higher at more rostral sites in the dPAG and decreased when NA was injected into the caudal portion of the dPAG. The responses to NA were markedly reduced in urethane-anaesthetized rats. The pressor response was potentiated by i.v. pretreatment with the ganglion blocker pentolinium and blocked by i.v. pretreatment with the vasopressin antagonist dTyr(CH2)5(Me)AVP. The results suggest that activation of noradrenergic receptors within the dPAG can evoke pressor responses, which are mediated by acute vasopressin release.