RESUMO

Insular cortex is a brain structure involved in the modulation of autonomic activity and cardiovascular function. The nitric oxide/cyclic guanosine-3',5'-monophosphate pathway is a prominent signaling mechanism in the central nervous system, controlling behavioral and physiological responses. Nevertheless, despite evidence regarding the presence of nitric oxide-synthesizing neurons in the insular cortex, its role in the control of autonomic and cardiovascular function has never been reported. Thus, the present study aimed to investigate the involvement of nitric oxide/cyclic guanosine-3',5'-monophosphate pathway mediated by neuronal nitric oxide synthase (nNOS) activation within the insular cortex in the modulation of baroreflex responses in unanesthetized rats. For this, we evaluated the effect of bilateral microinjection of either the nitric oxide scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase inhibitor Nω-Propyl-l-arginine or the soluble guanylate cyclase inhibitor ODQ into the insular cortex on the bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and the tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of either NPLA or carboxy-PTIO into the insular cortex increased the reflex bradycardic response, whereas the reflex tachycardia was decreased by these treatments. Bilateral microinjection of the soluble guanylate cyclase inhibitor into the insular cortex did not affect any parameter of baroreflex function evaluated. Overall, our findings provide evidence that insular cortex nitrergic signaling, acting via neuronal nitric oxide synthase, plays a prominent role in control of baroreflex function. However, control of reflex responses seems to be independent of soluble guanylate cyclase activation.

Assuntos

Barorreflexo/fisiologia , Córtex Cerebral/metabolismo , GMP Cíclico/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Benzoatos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/farmacologia , Masculino , Oxidiazóis/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos

RESUMO

Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson's animal models; Parkinson's history; Parkinson's and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

Assuntos

Humanos , Animais , Doença de Parkinson/tratamento farmacológico , Canabidiol/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Modelos Animais de Doenças , Estudos Clínicos como Assunto

RESUMO

Hippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal muscarinic receptors activation by acetylcholine might evoke nitric oxide synthesis, which is an important neuromodulator of cardiovascular responses. Thus, we hypothesize that cholinergic and nitrergic neurotransmission within the DH modulates the baroreflex and chemoreflex function. We have used vasoactive drugs (phenylephrine and sodium nitroprusside), and potassium cyanide infused peripherally to induce, respectively, baroreflex or chemoreflex responses in awake animals. Bilateral injection into the DH of the acetylcholinesterase inhibitor (neostigmine) reduced baroreflex responses. Meanwhile, the non-selective muscarinic receptor antagonist (atropine) or the M1-selective muscarinic receptor antagonist increased baroreflex responses (pirenzepine). Furthermore, the neuronal nitric oxide synthase inhibitor (N-propyl) or the intracellular NO scavenger (carboxy-PTIO) increased baroreflex responses, as well as the selective inhibitor of NO-sensitive guanylyl cyclase (ODQ), increased the baroreflex responses. Besides, bilateral administration of an ineffective dose of a neuronal nitric oxide synthase inhibitor abolished the reduction in the baroreflex responses evoked by an acetylcholinesterase inhibitor. On the other hand, we have demonstrated that hippocampal cholinergic neurotransmission did not influence the chemoreflex function. Taken together, our findings suggest that nNOS-derived nitric oxide in the DH participates in acetylcholine-evoked baroreflex responses.

Assuntos

Barorreflexo , Transmissão Sináptica , Animais , Colinérgicos , Hipocampo , Óxido Nítrico , Ratos , Ratos Wistar

RESUMO

Current pharmacotherapy of Parkinson's disease (PD) is palliative and unable to modify the progression of neurodegeneration. Treatments that can improve patients' quality of life with fewer side effects are needed, but not yet available. Cannabidiol (CBD), the major non-psychotomimetic constituent of cannabis, has received considerable research attention in the last decade. In this context, we aimed to critically review the literature on potential therapeutic effects of CBD in PD and discuss clinical and preclinical evidence supporting the putative neuroprotective mechanisms of CBD. We searched MEDLINE (via PubMed) for indexed articles published in English from inception to 2019. The following keywords were used: cannabis; cannabidiol and neuroprotection; endocannabinoids and basal ganglia; Parkinson's animal models; Parkinson's history; Parkinson's and cannabidiol. Few studies addressed the biological bases for the purported effects of CBD on PD. Six preclinical studies showed neuroprotective effects, while three targeted the antidyskinetic effects of CBD. Three human studies have tested CBD in patients with PD: an open-label study, a case series, and a randomized controlled trial. These studies reported therapeutic effects of CBD on non-motor symptoms. Additional research is needed to elucidate the potential effectiveness of CBD in PD and the underlying mechanisms involved.

Assuntos

Canabidiol/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Humanos

RESUMO

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.

Assuntos

Canabidiol/farmacologia , Nociceptividade/efeitos dos fármacos , Doença de Parkinson/fisiopatologia , Amidoidrolases/antagonistas & inibidores , Analgésicos/farmacologia , Animais , Benzamidas/farmacologia , Encéfalo/patologia , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Carbamatos/farmacologia , Celecoxib/farmacologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfina/farmacologia , Oxidopamina , Dor/tratamento farmacológico , Piperidinas/farmacologia , Pirazóis/farmacologia , Tienamicinas/farmacologia

RESUMO

GABAergic inhibitory input within the paraventricular hypothalamic nucleus (PVN) plays a key role in restraining sympathetic outflow. Although experimental evidence has shown depressed GABAA receptor function plus sympathoexcitation in hypertension and augmented GABA levels with reduced sympathetic activity after exercise training (T), the mechanisms underlying T-induced effects remain unclear. Here we investigated in T and sedentary (S) SHR and WKY: (1) time-course changes of hemodynamic parameters and PVN glutamic acid decarboxylase (GAD) isoforms' expression; (2) arterial pressure (AP) and heart rate (HR) responses, sympathetic/parasympathetic modulation of heart and vessels and baroreflex sensitivity to GABAA receptor blockade within the PVN. SHR-S versus WKY-S exhibited higher AP and HR, increased sympathetic reduced parasympathetic modulation, smaller baroreflex sensitivity, and reduced PVN GAD65 immunoreactivity. SHR-T and WKY-T showed prompt maintained increase (2-8 weeks) in GAD65 expression (responsible for GABA vesicular pool synthesis), which occurred simultaneously with HR reduction in SHR-T and preceded MAP fall in SHR-T and resting bradycardia in WKY-T. There was no change in GAD67 expression (mainly involved with GABA metabolic pool). Resting HR in both groups and basal MAP in SHR were negatively correlated with PVN GAD65 expression. Normalized baroreflex sensitivity and autonomic control observed only in SHR-T were due to recovery of GABAA receptor function into the PVN since bicuculline administration abolished these effects. Data indicated that training augments in both groups the expression/activity of GABAergic neurotransmission within presympathetic PVN neurons and restores GABAA receptors' function specifically in the SHR, therefore strengthening GABAergic modulation of sympathetic outflow in hypertension.

Assuntos

Glutamato Descarboxilase/genética , Hipertensão/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Esforço Físico , Receptores de GABA-A/metabolismo , Animais , Barorreflexo , Pressão Sanguínea , Glutamato Descarboxilase/metabolismo , Hipertensão/fisiopatologia , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Sistema Nervoso Simpático/fisiopatologia

RESUMO

The ventral medial prefrontal cortex (vMPFC) facilitates the cardiac baroreflex response through N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide (NO) formation by neuronal NO synthase (nNOS) and soluble guanylate cyclase (sGC) triggering. Glutamatergic transmission is modulated by the cannabinoid receptor type 1 (CB1) and transient receptor potential vanilloid type 1 (TRPV1) receptors, which may inhibit or stimulate glutamate release in the brain, respectively. Interestingly, vMPFC CB1 receptors decrease cardiac baroreflex responses, while TRPV1 channels facilitate them. Therefore, the hypothesis of the present study is that the vMPFC NMDA/NO pathway is regulated by both CB1 and TRPV1 receptors in the modulation of cardiac baroreflex activity. In order to test this assumption, we used male Wistar rats that had stainless steel guide cannulae bilaterally implanted in the vMPFC. Subsequently, a catheter was inserted into the femoral artery, for cardiovascular recordings, and into the femoral vein for assessing baroreflex activation. The increase in tachycardic and bradycardic responses observed after the microinjection of a CB1 receptors antagonist into the vMPFC was prevented by an NMDA antagonist as well as by the nNOS and sGC inhibition. NO extracellular scavenging also abolished these responses. These same pharmacological manipulations inhibited cardiac reflex enhancement induced by TRPV1 agonist injection into the area. Based on these results, we conclude that vMPFC CB1 and TRPV1 receptors inhibit or facilitate the cardiac baroreflex activity by stimulating or blocking the NMDA activation and NO synthesis.

Assuntos

Barorreflexo , Coração/fisiologia , Córtex Pré-Frontal/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Frequência Cardíaca , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Canais de Cátion TRPV/agonistas

RESUMO

Although it is well-established that severe poisoning by organophosphorus (OP) compounds strongly affects the cardiorespiratory system, the effects of sub-lethal exposure to these compounds on the neural control of cardiovascular function are poorly explored. The aim of this study was to evaluate the effects of acute sub-lethal exposure to chlorpyrifos (CPF), a commonly used OP insecticide, on three basic reflex mechanisms involved in blood pressure regulation, the peripheral chemoreflex, the baroreflex and the Bezold-Jarisch reflex. Adult male Wistar rats were injected intraperitoneally with a single dose of CPF (30 mg/kg) or saline (0.9%). 24 h after injections, cardiovascular reflexes were tested in awake rats. Potassium cyanide (KCN) and phenylbiguanide (PBG) were injected intravenously to activate the chemoreflex and the Bezold-Jarisch reflex, respectively. The baroreflex was activated by phenylephrine and sodium nitroprusside infusions. Blood samples were taken for measurements of butyrylcholinesterase (BChE) activity while acetylcholinesterase (AChE) activity was measured in brainstem samples. Animals treated with CPF presented signs of intoxication such as ataxia, tremor, lacrimation, salivation, tetany, urination and defecation. The hypertensive and the bradycardic responses of the chemoreflex as well as the hypotensive and bradycardic responses of the Bezold-Jarisch reflex were attenuated in CPF treated animals (P < 0.05). Concerning the baroreflex responses, CPF treatment reduced the bradycardia plateau, the range and the gain of the reflex (P < 0.05). Plasma BChE and brainstem AChE were both reduced significantly after CPF treatment (P < 0.05). Our results showed that acute sub-lethal exposure to CPF impairs the cardiovascular responses of homeostatic and defensive cardiovascular reflexes. These effects are associated with a marked inhibition of plasma BChE and brainstem AChE.

Assuntos

Barorreflexo/efeitos dos fármacos , Tronco Encefálico/efeitos dos fármacos , Clorpirifos/toxicidade , Acetilcolinesterase/sangue , Acetilcolinesterase/metabolismo , Animais , Tronco Encefálico/enzimologia , Butirilcolinesterase/sangue , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/toxicidade , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/metabolismo , Inseticidas/toxicidade , Masculino , Projetos Piloto , Ratos , Ratos Wistar , Testes de Toxicidade Aguda

RESUMO

The dorsal hippocampus (DH) is involved in the modulation of the cardiac baroreflex function. There is a wide expression of the NMDA and AMPA/Kainate receptors within the DH. Glutamate administration into the DH triggers both tachycardia and pressor responses. Moreover, GABAergic interneurons and endocannabinoid system play an important role in modulation of the activity of glutamatergic neurons within the DH. Therefore, the present work aimed to evaluate the involvement of the glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the DH in cardiac baroreflex function in rats. We have used the technique of vasoactive drugs infusion to build both sigmoidal curves and linear regressions to analyze the cardiac baroreflex function. Bilateral injection into the DH of DL-AP7, a NMDA receptor antagonist (10 or 50 nmol/500 nL), or NBQX, an AMPA/Kainate antagonist (100 nmol/ 500 nL), reduced the cardiac baroreflex function. On the other hand, bilateral injection of Bicuculline, a GABAA receptor antagonist (1 nmol/500 nL), or AM251, a CB1 receptor antagonist (10 or 100 pmol/500 nL), increased the cardiac baroreflex function. Furthermore, 1 nmol/500 nL of the NMDA receptor antagonist, when administrated alone, was ineffective to change baroreflex function, but it was able to inhibit the alteration in the cardiac baroreflex function elicited by the dose of 100 pmol/500 nL of the CB1 receptor antagonist. Taken together, these findings suggest that glutamatergic, GABAergic, and endocannabinoid neurotransmissions interact each other within the DH to modulate the cardiac baroreflex function.

Assuntos

Barorreflexo , Coração/fisiologia , Hipocampo/metabolismo , Receptores de Canabinoides/metabolismo , Receptores de GABA/metabolismo , Receptores de Glutamato/metabolismo , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Masculino , Ratos , Ratos Wistar , Transmissão Sináptica

RESUMO

NEW FINDINGS: What is the central question of this study? Classically, areas of the brainstem are involved in the cardiac baroreceptor reflex. However, forebrain areas, such as the hippocampus, may also modulate the cardiac baroreflex function. What is the main finding and its importance? According to the hippocampal subarea recruited dorsoventrally, the baroreflex function can be either facilitated or inhibited. These results are according to the new topographical division proposed for the hippocampus, i.e. it can be divided into functionally and anatomically different regions along its dorsoventral axis. From a neuroanatomical point of view, we may split the hippocampal formation into the dorsal (DH) and ventral hippocampus (VH). Although the basic intrinsic circuitry of the hippocampus seems to be maintained throughout its longitudinal axis, dorsal and ventral portions connect differently with cortical and subcortical areas and express different gene patterns, being functionally distinct. Differential stimulation of the DH or VH can evoke either an increase or a decrease in blood pressure, heart rate and sympathetic activity. However, to the best of our knowledge, specific involvement of the hippocampus and its different subareas in the baroreflex function remains to be investigated. In the present work, therefore, we evaluated the involvement of hippocampal subareas arranged on the dorsoventral axis in cardiac baroreflex modulation. Our results suggest that inhibition of hippocampal subareas by CoCl2 , a calcium-dependent synaptic neurotransmission blocker, differentially affects baroreflex sensitivity; administration of CoCl2 into the DH increased cardiac baroreflex function, whereas it diminished cardiac baroreflex function when administered into the VH. In contrast, administration of CoCl2 into intermediate portions of the hippocampus did not affect the baroreflex response. Our findings suggest that the hippocampus influences baroreflex function according to the hippocampal subarea recruited dorsoventrally.

Assuntos

Barorreflexo/fisiologia , Coração/fisiologia , Hipocampo/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cobalto/farmacologia , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia

RESUMO

Exposure to stressful situations is one of the risk factors for the precipitation of several psychiatric disorders, including Major Depressive Disorder, Posttraumatic Stress Disorder and Schizophrenia. The hippocampal formation is a forebrain structure highly associated with emotional, learning and memory processes; being particularly vulnerable to stress. Exposure to stressful stimuli leads to neuroplastic changes and imbalance between inhibitory/excitatory networks. These changes have been associated with an impaired hippocampal function. Endocannabinoids (eCB) are one of the main systems controlling both excitatory and inhibitory neurotransmission, as well as neuroplasticity within the hippocampus. Cannabinoids receptors are highly expressed in the hippocampus, and several lines of evidence suggest that facilitation of cannabinoid signaling within this brain region prevents stress-induced behavioral changes. Also, chronic stress modulates hippocampal CB1 receptors expression and endocannabinoid levels. Moreover, cannabinoids participate in mechanisms related to synaptic plasticity and adult neurogenesis. Here, we discussed the main findings supporting the involvement of hippocampal cannabinoid neurotransmission in stress-induced behavioral and neuroplastic changes.

RESUMO

Baroreflex activity is a neural mechanism responsible for short-term adjustments in blood pressure (BP). Several supramedullary areas, which send projections to the medulla, are able to control this reflex. In this context, the ventrolateral part of the periaqueductal grey matter (vlPAG), which is a mesencephalic structure, has been suggested to regulate the cardiovascular system. However, its involvement in baroreflex control has never been addressed. Therefore, our hypothesis is that the vlPAG neurotransmission is involved in baroreflex cardiac activity. Male Wistar rats had stainless steel guide cannulae unilaterally or bilaterally implanted in the vlPAG. Afterward, a catheter was inserted into the femoral artery for BP and HR recording. A second catheter was implanted into the femoral vein for baroreflex activation. When the nonselective synaptic blocker cobalt chloride (CoCl2 ) was unilaterally injected into the vlPAG, in either the left or the right hemisphere, it increased the tachycardic response to baroreflex activation. However, when CoCl2 was bilaterally microinjected into the vlPAG it decreased the tachycardic response to baroreflex stimulation. This work shows that vlPAG neurotransmission is involved in modulation of the tachycardic response of the baroreflex. Moreover, we suggest that the interconnections between the vlPAG of both hemispheres are activated during baroreflex stimulation. In this way, our work helps to improve the understanding about brain-heart circuitry control, emphasizing the role of the autonomic nervous system in such modulation.

Assuntos

Barorreflexo , Coração/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Transmissão Sináptica , Animais , Pressão Sanguínea , Coração/inervação , Frequência Cardíaca , Masculino , Ratos , Ratos Wistar

RESUMO

NEW FINDINGS: What is the central question of this study? Does reversible synaptic inactivation by CoCl2 in the dorsal (DH) or ventral (VH) portions of the hippocampus have a modulatory effect on cardiovascular and respiratory responses evoked by chemoreflex activation in awake rats? What is the main finding and its importance? Using i.v. infusion of KCN to activate the peripheral chemoreflex before and after microinjection of CoCl2 into VH, we showed that the bradycardic response was increased, but not the pressor and tachypnoeic responses even if the tidal volume had been increased. Thus, VH but not DH may be involved in the modulation of the parasympathoexcitatory component of the peripheral chemoreflex. In rats, peripheral chemoreflex activation evokes pressor and bradycardic responses as well as a tachypnoeic response. Studies have shown that limbic structures, such as the hippocampus, can modulate autonomic reflexes. Evidence suggests that the dorsal (DH) and the ventral (VH) portions of the hippocampus are structurally and functionally distinct; therefore, in the present study we tested the hypothesis that local neurotransmission of the DH and VH are involved in the neural pathways of the cardiovascular and ventilatory responses to chemoreflex activation. Thus, the goal of the present study was to compare the chemoreflex responses elicited by i.v. injection of KCN (40 µg per rat) in awake rats before and after DH and VH synaptic transmission was temporarily inhibited by bilateral microinjections of 500 nl of the unspecific synapse blocker, CoCl2 (1  mm). Bilateral inhibition of VH, but not DH, 10 min before KCN infusion was able to enhance the bradycardic response (P < 0.05), with no changes in the typical pressor and tachypnoeic responses evoked by chemoreflex activation (P > 0.05). Furthermore, the tidal volume was significantly increased (P < 0.05) even though no other respiratory parameter had been significantly changed (P > 0.05), suggesting that VH can exert a tonic modulatory action on tidal volume. Therefore, the present study reports, for the first time, that DH neurotransmission did not exert an influence on chemoreflex responses, whereas VH mediates, at least in part, the parasympathoexcitatory component of the peripheral chemoreflex.

Assuntos

Sistema Cardiovascular/fisiopatologia , Células Quimiorreceptoras/fisiologia , Frequência Cardíaca/fisiologia , Hipocampo/fisiologia , Sistema Nervoso Periférico/fisiologia , Reflexo/fisiologia , Vigília/fisiologia , Animais , Bradicardia/fisiopatologia , Masculino , Microinjeções/métodos , Ratos , Ratos Wistar , Transmissão Sináptica/fisiologia

RESUMO

The medial amygdaloid nucleus (MeA) is involved in cardiovascular control. In the present study we report the effect of MeA pharmacological ablations caused by bilateral microinjections of the nonselective synaptic blocker CoCl2 on cardiac baroreflex responses in rats. MeA synaptic inhibition evoked by local bilateral microinjection of 100 nL of CoCl2 (1 mM) did not affect blood pressure or heart rate baseline, suggesting no tonic MeA influence on resting cardiovascular parameters. However, 10 min after CoCl2 microinjection into the MeA of male Wistar rats, the reflex bradycardic response evoked by intravenous infusion of phenylephrine was significantly enhanced when compared with the reflex bradycardic response observed before CoCl2. The treatment did not affect the tachycardic responses to the intravenous infusion of sodium nitroprusside (SNP). Baroreflex activity returned to control values 60 min after CoCl2 microinjections, confirming a reversible blockade. The present results indicate an involvement of the MeA in baroreflex modulation, suggesting that synapses in the MeA have an inhibitory influence on the bradycardic component of the baroreflex in conscious rats.

Assuntos

Barorreflexo/fisiologia , Complexo Nuclear Corticomedial/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Bradicardia/fisiopatologia , Fármacos do Sistema Nervoso Central/farmacologia , Cobalto/farmacologia , Estado de Consciência/fisiologia , Complexo Nuclear Corticomedial/efeitos dos fármacos , Masculino , Nitroprussiato/farmacologia , Ratos Wistar , Taquicardia/fisiopatologia , Vasodilatadores/farmacologia

RESUMO

Neural reflex mechanisms, such as the baroreflex, are involved in regulating cardiovascular system activity. Previous results showed that the ventral portion of the medial prefrontal cortex (vMPFC) is involved in modulation only of the cardiac baroreflex bradycardic component. Moreover, vMPFC N-methyl-D-aspartate (NMDA) receptors modulate the bradycardia baroreflex, but the baroreflex tachycardic component has not been investigated. Furthermore, glutamatergic neurotransmission into the vMPFC is involved in activation of the cardiac sympathetic and parasympathetic nervous system. Finally, it has been demonstrated that glutamatergic neurotransmission into the vMPFC can be modulated by the endocannabinoid system and that activation of the CB1 cannabinoid receptor by anandamide, an endocannabinoid, can decrease both cardiac baroreflex bradycardic and tachycardic responses. Thus, there is the possibility that glutamatergic neurotransmission into the vMPFC does not modulate only the cardiac bradycardic component of the baroreflex. Therefore, the present study investigated whether glutamatergic neurotransmission into the vMPFC modulates both cardiac baroreflex bradycardic and tachycardic responses. We found that vMPFC bilateral microinjection of the NMDA receptor antagonist AP7 (4 nmol/200 nl), of a selective inhibitor of neuronal nitric oxide (NO) synthase N-propyl (0.08 nmol/200 nl), of the NO scavenger carboxy-PTIO (2 nmol/200 nl), or of the NO-sensitive guanylate cyclase ODQ (2 nmol/200 nl) decreased the baroreflex activity in unanesthetized rats. Therefore, our results demonstrate the participation of NMDA receptors, production of NO, and activation of guanylate cyclase in the vMPFC in the modulation of both cardiac baroreflex bradycardic and tachycardic responses.

Assuntos

Barorreflexo/fisiologia , Bradicardia/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Taquicardia/metabolismo , Animais , Sistema Nervoso Autônomo/fisiologia , GMP Cíclico/metabolismo , Guanilato Ciclase/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia

RESUMO

We hypothesize that a local ATP-NO-NMDA glutamate receptor interaction in the paraventricular nucleus (PVN) modulates the baseline mean arterial pressure and heart rate in unanaesthetized rats. The microinjection of α,ß-methylene ATP [methyl ATP; 0.06, 0.12 and 1.2 nmol (100 nl)(-1)] into the PVN caused pressor and tachycardiac responses. Cardiovascular responses evoked by methyl ATP [0.12 nmol (100 nl)(-1)] in the PVN were blocked by pretreatment with the ganglion blocker pentolinium (5 mg kg(-1) i.v.). Also, responses to the injection of methyl ATP [0.12 nmol (100 nl)(-1)] into the PVN were reduced by pretreatment with the selective P2 purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid [0.5 nmol (100 nl)(-1)], the neuronal NO synthase inhibitor N(ω)-propyl-l-arginine [0.04 nmol (100 nl)(-1)] or the selective NMDA glutamate receptor antagonist LY235959 [2 nmol (100 nl)(-1)]. In addition, an injection of the NO donor sodium nitroprusside [27 nmol (100 nl)(-1)] into the PVN caused similar cardiovascular responses to those observed after methyl ATP, which were blocked by local pretreatment with LY235959. Therefore, the present results suggest that cardiovascular responses evoked by methyl ATP in the PVN involve a local production of NO, which promotes local glutamate release and activation of NMDA receptors that are probably located in pre-autonomic parvocellular neurons, leading to sympathetic nervous system stimulation.

Assuntos

Trifosfato de Adenosina/análogos & derivados , Óxido Nítrico/fisiologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/fisiologia , Trifosfato de Adenosina/farmacologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores Ganglionares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Microinjeções , Óxido Nítrico/biossíntese , Nitroprussiato/farmacologia , Antagonistas do Receptor Purinérgico P2/farmacologia , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Quinazolinonas , Ratos , Ratos Wistar , Vigília

RESUMO

Neural reflex mechanisms, such as the baroreflex, are involved in the regulation of cardiovascular system activity. Previous results from our group (Resstel LB, Correa FM. Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex. Eur J Neurosci 23: 481-488, 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB(1) receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB(1) receptors modulate baroreflex activity. We found that bilateral microinjection of the CB(1) receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB(1) receptors, which modulate local glutamate release.

Assuntos

Barorreflexo/fisiologia , Moduladores de Receptores de Canabinoides/fisiologia , Endocanabinoides , Córtex Pré-Frontal/fisiologia , Receptor CB1 de Canabinoide/fisiologia , Amidoidrolases/antagonistas & inibidores , Animais , Ácidos Araquidônicos/farmacologia , Barorreflexo/efeitos dos fármacos , Benzamidas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Carbamatos/farmacologia , Ácido Glutâmico/metabolismo , Masculino , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores

RESUMO

A luxaçäo congenita de ombro é uma entidade näo comum. Apesar disso, há alguns escritos e relatos a esse respeito, todos deixando transparecer a dúvida entre o limite da verdadeira luxaçäo congênita de ombro e aquela associada a alguma outra anormalidade. Neste traalho, foi acompanhado e estudado um paciente com luxaçäo congênita bilateral de ombro, com a finalidade de procurar estabelecer o real conceito da patologia. Os autores concluíram, através de revisäo de literatura e acompanhamento do caso, que a luxaçäo congênita de ombro verdadeira é aquela em que há a quase constante bilateralidade; a absoluta ausência de lesöes neuromusculares associadas; a funcionalidade articular bem conservada, na qual a presença de frouxidäo capsuloligamentar permite ao ombro movimentos maiores e mais amplos que o normal, com conseqüente instabilidade da articulaçäo; o aplanamento da fossa glenóidea ao exame radiográfico; e a redutibilidade manual fácil da deformidade, que se reproduz imediatamente, uma vez o membro seja abandonado

Assuntos

Humanos , Masculino , Recém-Nascido , Luxação do Ombro/congênito , Luxação do Ombro/diagnóstico