Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
1.
Pflugers Arch ; 476(3): 351-364, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38228895

RESUMO

Despite the importance of physiological responses to stress in a short-term, chronically these adjustments may be harmful and lead to diseases, including cardiovascular diseases. The lateral hypothalamus (LH) has been reported to be involved in expression of physiological and behavioral responses to stress, but the local neurochemical mechanisms involved are not completely described. The corticotropin-releasing factor (CRF) neurotransmission is a prominent brain neurochemical system implicated in the physiological and behavioral changes induced by aversive threats. Furthermore, chronic exposure to aversive situations affects the CRF neurotransmission in brain regions involved in stress responses. Therefore, in this study, we evaluated the influence of CRF neurotransmission in the LH on changes in cardiovascular function and baroreflex activity induced by chronic variable stress (CVS). We identified that CVS enhanced baseline arterial pressure and impaired baroreflex function, which were followed by increased expression of CRF2, but not CRF1, receptor expression within the LH. Local microinjection of either CRF1 or CRF2 receptor antagonist within the LH inhibited the baroreflex impairment caused by CVS, but without affecting the mild hypertension. Taken together, the findings documented in this study suggest that LH CRF neurotransmission participates in the baroreflex impairment related to chronic stress exposure.


Assuntos
Hormônio Liberador da Corticotropina , Região Hipotalâmica Lateral , Ratos , Animais , Hormônio Liberador da Corticotropina/metabolismo , Hormônio Liberador da Corticotropina/farmacologia , Região Hipotalâmica Lateral/metabolismo , Barorreflexo , Encéfalo/metabolismo , Transmissão Sináptica
2.
Pflugers Arch ; 472(10): 1495-1506, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32827263

RESUMO

We investigated the spontaneous recovery, time course, and the influence of the time of day on the habituation of the cardiovascular responses with repeated exposure to restraint stress in male rats. Habituation of the corticosterone response to repeated restraint stress was also evaluated. The circulating corticosterone response decreased during both the stress and recovery periods of the tenth session of restraint. Habituation of the cardiovascular responses was identified as a faster return to baseline values of the heart rate (HR) and blood pressure (BP) during the recovery period of the tenth session of restraint. Habituation of the HR and BP was still observed after 10 days of discontinuation of the repeated exposure to restraint stress. However, spontaneous recovery of habituated responses was observed 20 days after the final restraint stress session. Time course analysis revealed decreased HR response during the recovery period of the third restraint session, without further reduction on the fifth, seventh, and tenth sessions. Decreased BP response was identified on the third and fifth sessions, whereas reduced tail skin temperature response was observed only on the fifth and seventh sessions. Regarding the time of day, habituation of the tachycardiac response was identified at the tenth session when repeated restraint stress was performed in the morning and night periods, but not in the afternoon. These findings provided evidence of spontaneous recovery of the habituation of cardiovascular responses to repeated restraint stress. Moreover, cardiovascular habituation was dependent on the number of trials and time of day.


Assuntos
Pressão Sanguínea , Ritmo Circadiano , Habituação Psicofisiológica , Frequência Cardíaca , Estresse Psicológico/fisiopatologia , Animais , Corticosterona/sangue , Masculino , Ratos , Ratos Wistar , Restrição Física/efeitos adversos , Temperatura Cutânea , Estresse Psicológico/etiologia
3.
Nitric Oxide ; 94: 114-124, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759128

RESUMO

Increased nitric oxide (NO) levels have been identified in the hippocampus of animals subjected to social isolation. However, a role of this change in behavioral and physiological changes evoked by isolation has never been evaluated. Thus, this study investigated the involvement of nitrergic neurotransmission acting via the neuronal isoform of nitric oxide synthase (nNOS) within the dorsal hippocampus in behavioral and cardiovascular changes in isolated reared rats. For this, male rats were isolated from weaning at 21 days postnatal for 40 days. We identified that social isolation increased hippocampal NO formation and nNOS expression. Besides, anxiogenic- and depressive-like effect identified in isolated animals were not affected by intra-hippocampal microinjection of either the NO scavenger carboxy-PTIO or the selective nNOS inhibitor Nω-Propyl-l-arginine (NPLA). Isolation also increased basal arterial pressure, impaired the baroreflex function and decreased the tachycardia to restraint stress. The effects in restraint-evoked tachycardia were inhibited by hippocampal treatment with either carboxy-PTIO or NPLA. Intra-hippocampal administration of either carboxy-PTIO or NPLA also enhanced the pressor response to restraint in isolated, but not in control animals. Taken together, these findings indicate that increased NO release within the dorsal hippocampus is involved in impairment of cardiovascular responses to a novel stressor, but not in behavioral effects and baroreflex changes, evoked by social isolation. Furthermore, exposure to this stressor evokes the emergence of an inhibitory role of hippocampal nNOS activation in cardiovascular changes to a novel stressor, which might constitute a prominent adaptive response.


Assuntos
Comportamento Animal , Sistema Cardiovascular/metabolismo , Hipocampo/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/metabolismo , Estresse Psicológico , Animais , Sistema Cardiovascular/patologia , Doença Crônica , Masculino , Ratos , Ratos Wistar , Transmissão Sináptica
4.
J Exp Biol ; 223(Pt 8)2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32205360

RESUMO

This study evaluated the effect of exposure to either a chronic variable stress (CVS) protocol or social isolation, as well as treadmill exercise training, in the habituation of the cardiovascular response upon repeated exposure to restraint stress in rats. The habituation of the corticosterone response to repeated restraint stress was also evaluated. For this, animals were subjected to either acute or 10 daily sessions of 60 min of restraint stress. CVS and social isolation protocols lasted for 10 consecutive days, whereas treadmill training was performed for 1 h per day, 5 days per week for 8 weeks. We observed that the increase in serum corticosterone was reduced during both the stress and the recovery period of the 10th session of restraint. Habituation of the cardiovascular response was identified in terms of a faster return of heart rate to baseline values during the recovery period of the 10th session of restraint. The increase in blood pressure and the decrease in tail skin temperature were similar at the 1st and 10th session of restraint. Exposure to CVS, social isolation or treadmill exercise training inhibited the habituation of the restraint-evoked tachycardia. Additionally, CVS increased the blood pressure response at the 10th session of restraint, whereas social isolation enhanced both the tachycardia during the first session and the drop in skin temperature at the 10th session of restraint. Taken together, these findings provide new evidence that pathologies evoked by stress might be related to impairment in the habituation process to homotypic stressors.


Assuntos
Sistema Cardiovascular , Habituação Psicofisiológica , Animais , Corticosterona , Frequência Cardíaca , Sistema Hipotálamo-Hipofisário , Ratos , Restrição Física , Estresse Psicológico
5.
Stress ; 22(1): 151-161, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30632936

RESUMO

Habituation of cardiovascular responses upon repeated exposure to stress is controversial. Hence, we hypothesized that habituation of cardiovascular stress responses is influenced by length, frequency, and number of stress sessions in male Wistar rats. Blood pressure and heart rate were recorded via femoral artery catheterization and the tail cutaneous temperature was evaluated using a thermal imager. We observed a faster return of heart rate to baseline values during the post-stress period of the 10th daily session in rats subjected to either 60 (n = 8) or 120 min (n = 7), but not 30 min (n = 7), of restraint. Daily sessions of 120 min also decreased blood pressure during the recovery of the 10th session. The faster return of heart rate to baseline values during the post-stress period at the 10th session in rats exposed to daily 60 min sessions (n = 9) was not identified at the 5th (n = 9) and 20th (n = 9) sessions. Regarding frequency, the tachycardia during the 10th session was enhanced in rats subjected to 60 min of restraint presented every other day (n = 9) and decreased in rats subjected to a protocol of five daily sessions followed by two resting days (n = 9). Thirty-minute sessions of restraint presented twice a day (n = 9) and a protocol of three daily sessions followed by a resting day (n = 9) did not affect the restraint-evoked cardiovascular responses at the 10th session. These results provide evidence of habituation of the cardiovascular responses upon repeated exposure to restraint stress, which is dependent on length, frequency, and number of trials. Lay summary Cardiovascular responses decrease upon repeated exposure to restraint stress. The decrease in cardiovascular stress responses is observed as a faster return to basal values during the post-stress period. The cardiovascular stress response decrease (habituation to stress) is dependent on the length, frequency, and number of stress sessions.


Assuntos
Sistema Cardiovascular/fisiopatologia , Restrição Física/fisiologia , Estresse Psicológico/fisiopatologia , Animais , Corticosterona/sangue , Masculino , Ratos , Ratos Wistar
6.
Eur J Neurosci ; 46(2): 1805-1812, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28612996

RESUMO

The baroreflex is an important blood pressure regulating mechanism. The bed nucleus of stria terminalis (BNST) modulates the baroreflex function. However, the local BNST neurochemical mechanisms involved in control of baroreflex responses are not completely understood. Therefore, in this study, we investigated the involvement of corticotropin-releasing factor (CRF) receptors within the BNST in baroreflex control of heart rate in unanesthetized rats. For this, we evaluated effects of bilateral microinjection into the BNST of either the selective CRF1 receptor antagonist CP376395 (5 nmol/100 nL) or the selective CRF2 receptor antagonist antisauvagine-30 (5 nmol/100 nL) in bradycardiac response evoked by blood pressure increases caused by intravenous infusion of phenylephrine as well as tachycardiac response to blood pressure decrease caused by intravenous infusion of sodium nitroprusside. Bilateral microinjection of CP376395 into the BNST decreased the baroreflex bradycardiac response without affecting the reflex tachycardia. Conversely, BNST treatment with antisauvagine-30 decreased heart rate response during blood pressure drop without affecting the reflex bradycardia. Overall, these findings provide evidence of an involvement of CRF neurotransmission within the BNST in baroreflex activity. Nevertheless, data indicate that local CRF1 and CRF2 receptors differently modulate the baroreflex control of heart rate.


Assuntos
Barorreflexo/fisiologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Núcleos Septais/metabolismo , Aminopiridinas/farmacologia , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Fármacos Cardiovasculares/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Microinjeções , Nitroprussiato/farmacologia , Fragmentos de Peptídeos/farmacologia , Fenilefrina/farmacologia , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Núcleos Septais/efeitos dos fármacos
7.
Pharmacol Res ; 95-96: 53-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25829333

RESUMO

The corticotropin-releasing factor (CRF) is involved in behavioral and physiological responses to emotional stress through its action in several limbic structures, including the bed nucleus of the stria terminalis (BNST). Nevertheless, the role of CRF1 and CRF2 receptors in the BNST in cardiovascular adjustments during aversive threat is unknown. Therefore, in the present study we investigated the involvement of CRF receptors within the BNST in cardiovascular responses evoked by acute restraint stress in rats. For this, we evaluated the effects of bilateral treatment of the BNST with selective agonists and antagonists of either CRF1 or CRF2 receptors in the arterial pressure and heart rate increase and the decrease in tail skin temperature induced by restraint stress. Microinjection of the selective CRF1 receptor antagonist CP376395 into the BNST reduced the pressor and tachycardiac responses caused by restraint. Conversely, BNST treatment with the selective CRF1 receptor agonist CRF increased restraint-evoked arterial pressure and HR responses and reduced the fall in tail skin temperature response. All effects of CRF were inhibited by local BNST pretreatment with CP376395. The selective CRF2 receptor antagonist antisalvagine-30 reduced the arterial pressure increase and the fall in tail skin temperature. The selective CRF2 receptor agonist urocortin-3 increased restraint-evoked pressor and tachycardiac responses and reduced the drop in cutaneous temperature. All effects of urocortin-3 were abolished by local BNST pretreatment with antisalvagine-30. These findings indicate an involvement of both CRF1 and CRF2 receptors in the BNST in cardiovascular adjustments during emotional stress.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Núcleos Septais/metabolismo , Estresse Psicológico/metabolismo , Aminopiridinas/farmacologia , Animais , Hormônio Liberador da Corticotropina/farmacologia , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/agonistas , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Restrição Física , Núcleos Septais/efeitos dos fármacos , Temperatura Cutânea/efeitos dos fármacos , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Taquicardia/etiologia , Urocortinas/farmacologia
8.
J Exerc Sci Fit ; 13(1): 1-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29541092

RESUMO

BACKGROUND/OBJECTIVE: This study evaluated the influence of sex on changes in cytokines, heat shock proteins (HSPs), and oxidative stress in response to a single bout of total body resistance exercise. METHODS: Sixteen healthy volunteers (8 men and 8 women), active and recreationally trained in resistance exercise, were subjected to a single bout of total body resistance exercise (3 × 8-10 repetition maximum, 10 exercises, rests periods of 90-120 seconds). Serum creatine kinase (CK), interleukin (IL)-6, IL-10, tumor necrosis factor-α, HSP60, HSP70, thiobarbituric acid reactive substance, and reduced glutathione were assessed at pre-protocol, and 1 hour, 4 hours, and 24 hours post-protocol. RESULTS: Both men and women had a similar increase in CK (p < 0.05) activity at 24 hours post-exercise. Significant sex differences were observed for IL-6. In the men, an increase from baseline was noted at 1 hour for IL-6. In women, an increase from baseline was noted at 4 hours only for IL-6. There was a significant correlation between peak IL-6 blood level and CK level at 24 hours only in the women. No significant changes were observed in IL-10, tumor necrosis factor-α, HSP60, HSP70, thiobarbituric acid reactive substance, and reduced glutathione. CONCLUSION: Acute total body resistance exercise altered circulating levels of IL-6 and sex differences existed in the temporal pattern and magnitude of this response.

9.
Neuropharmacology ; 212: 109061, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35452627

RESUMO

We investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the lateral hypothalamus (LH) in cardiovascular and anxiogenic-like responses evoked by acute and repeated restraint stress in rats. For this, animals were subjected to intra-LH microinjection of a selective CRF1 (CP376395) or CRF2 (antisauvagine-30) receptor antagonist before either an acute or the 10th session of restraint stress. Restraint-evoked arterial pressure and heart rate increases, tail skin temperature decrease and anxiogenic-like effect in the elevated plus maze (EPM) were evaluated. We also assessed the effect of 10 daily sessions of restraint on expression of CRF1 and CRF2 receptors within the LH. We identified that antagonism of either CRF1 or CRF2 receptor within the LH decreased the tachycardia during both the acute and 10th session of restraint, but the effect of the CRF1 receptor antagonist was more pronounced during the 10th session. Acute restraint stress also caused anxiogenic-like effect, and this response was inhibited in animals treated with either CP376395 or antisauvagine-30. Anxiety-like behaviors were not changed following the 10th session of restraint, and pharmacological treatments did not affect the behavior in the EPM in chronically stressed animals. Repeated restraint also did not change the level of the CRF receptors within the LH. Taken together, the findings indicate that CRF1 and CRF2 receptors within the LH are involved in tachycardic and anxiogenic-like responses to aversive stimuli. Control of tachycardia by the CRF1 receptor is sensitized by previous stressful experience, and this effect seems to be independent of changes in expression of the receptor.


Assuntos
Hormônio Liberador da Corticotropina , Região Hipotalâmica Lateral , Receptores de Hormônio Liberador da Corticotropina , Animais , Hormônio Liberador da Corticotropina/metabolismo , Região Hipotalâmica Lateral/metabolismo , Ratos , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Restrição Física , Taquicardia/tratamento farmacológico
10.
Front Neurosci ; 16: 878927, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620667

RESUMO

The insular cortex (IC) has been described as a part of the central network implicated in the integration and processing of limbic information, being related to the behavioral and physiological responses to stressful events. Besides, a site-specific control of physiological functions has been reported along the rostrocaudal axis of the IC. However, a functional topography of the IC in the regulation of stress responses has never been reported. Therefore, this study aimed to investigate the impact of acute restraint stress in neuronal activation at different sites along the rostrocaudal axis of the IC. Furthermore, we evaluated the involvement of IC rostrocaudal subregions in the cardiovascular responses to acute restraint stress. We observed that an acute session of restraint stress increased the number of Fos-immunoreactive cells in the rostral posterior region of the IC, while fewer activated cells were identified in the anterior and caudal posterior regions. Bilateral injection of the non-selective synaptic inhibitor CoCl2 into the anterior region of the IC did not affect the blood pressure and heart rate increases and the sympathetically mediated cutaneous vasoconstriction to acute restraint stress. However, synaptic ablation of the rostral posterior IC decreased the restraint-evoked arterial pressure increase, whereas tachycardia was reduced in animals in which the caudal posterior IC was inhibited. Taken together, these pieces of evidence indicate a site-specific regulation of cardiovascular stress response along the rostrocaudal axis of the IC.

11.
Artigo em Inglês | MEDLINE | ID: mdl-35798175

RESUMO

The insular cortex (IC) is a brain structure involved in physiological and behavioural responses during stressful events. However, the local neurochemical mechanisms involved in control of stress responses by the IC are poorly understood. Thus, this study aimed to investigate the involvement of glutamatergic neurotransmission within the IC in cardiovascular, autonomic and neuroendocrine responses to an acute session of restraint stress. For this, the selective NMDA glutamate receptor antagonist LY235959 (1 nmol/100 nL) or the selective non-NMDA glutamate receptor antagonist NBQX (1 nmol/100 nL) were microinjected into the IC 10 min before the onset of the 60 min session of restraint stress. We observed that the antagonism of NMDA receptors within the IC enhanced the restraint-evoked increase in arterial pressure and heart rate, while blockade of non-NMDA receptors did not affect these cardiovascular responses. Spontaneous baroreflex analysis demonstrated that microinjection of LY235959 into the IC decreased baroreflex activity during restraint stress. The decrease in tail skin temperature during restraint stress was shifted to an increase in animals treated with the NMDA receptor antagonist. Nevertheless, the blockade of either NMDA or non-NMDA glutamate receptors within the IC did not affect the increase in circulating corticosterone levels during restraint stress. Overall, our findings provide evidence that IC glutamatergic neurotransmission, acting via local NMDA receptors, plays a prominent role in the control of autonomic and cardiovascular responses to restraint stress, but without affecting neuroendocrine adjustments.


Assuntos
Antagonistas de Aminoácidos Excitatórios , Receptores de N-Metil-D-Aspartato , Animais , Pressão Sanguínea , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico , Frequência Cardíaca/fisiologia , Córtex Insular , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Restrição Física
12.
Artigo em Inglês | MEDLINE | ID: mdl-32535028

RESUMO

Chronic exposure to adverse events has been proposed as a prominent factor involved in etiology and progression of cardiovascular dysfunctions in humans and animals. However, the neurobiological mechanisms involved are still poorly understood. In this sense, chronic stress has been reported to evoke neuroplasticity in corticotropin-releasing factor (CRF) neurotransmission in several limbic structures, including the bed nucleus of the stria terminalis. However, a possible involvement of BNST CRF neurotransmission in cardiovascular dysfunctions evoked by chronic stress has never been reported. Thus, this study investigated the involvement of CRF1 and CRF2 receptors within the BNST in cardiovascular changes evoked by chronic stress in rats. We identified that exposure to a 10-day chronic variable stress (CVS) protocol decreased expression of both CRF1 and CRF2 receptors within the BNST. These effects were followed by increased arterial pressure and impairment of baroreflex function, but without changes on heart rate. Bilateral microinjection of either the selective CRF1 receptor antagonist CP376395 or the selective CRF2 receptor antagonist antisauvagine-30 into the BNST did not affect CVS-evoked arterial pressure increase. Nevertheless, BNST treatment with CP376395 decreased both tachycardic and bradycardic responses of the baroreflex in non-stressed rats; but these effects were not identified in chronically stressed animals. BNST pharmacological treatment with antisauvagine-30 decreased the reflex tachycardia in control animals, whereas reflex bradycardic response was increased in CVS animals. Altogether, the results reported in the present study indicate that down regulation of both CRF1 and CRF2 receptors within the BNST is involved in baroreflex impairment evoked by chronic stress.


Assuntos
Barorreflexo/fisiologia , Receptores de Hormônio Liberador da Corticotropina/genética , Núcleos Septais/metabolismo , Aminopiridinas/farmacologia , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Núcleos Septais/efeitos dos fármacos , Estresse Psicológico/genética , Estresse Psicológico/metabolismo
13.
Brain Res Bull ; 166: 102-109, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33227387

RESUMO

The lateral hypothalamus (LH) is implicated in the physiological and behavioral responses during stressful events. However, the local neurochemical mechanisms related to control of stress responses by this hypothalamic area are not completely understood. Therefore, in this study we evaluated the involvement of CRFergic neurotransmission acting through the CRF1 receptor within the LH in cardiovascular responses evoked by an acute session of restraint stress in rats. For this, we investigated the effect of bilateral microinjection of different doses (0.01, 0.1 and 1 nmol/100 nL) of the selective CRF1 receptor antagonist CP376395 into the LH on arterial pressure and heart rate increases and decrease in tail skin temperature evoked by acute restraint stress. We found that all doses of the CRF1 receptor antagonist microinjected into the LH decreased the restraint-evoked tachycardia, but without affecting the arterial pressure and tail skin temperature responses. Additionally, treatment of the LH with CP376395 at the doses of 0.1 and 1 nmol/100 nL increased the basal values of both heart rate and arterial pressure, whereas the dose of 0.1 nmol/100 nL decreased the skin temperature. Taken together, these findings indicate that CRFergic neurotransmission in the LH, acting through activation of local CRF1 receptors, plays a facilitatory role in the tachycardia observed during aversive threats, but without affecting the pressor and tail skin temperature responses. Our results also provide evidence that LH CRFergic neurotransmission in involved in tonic maintenance of cardiovascular function.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Região Hipotalâmica Lateral/fisiologia , Angústia Psicológica , Transmissão Sináptica/fisiologia , Taquicardia/fisiopatologia , Animais , Frequência Cardíaca/fisiologia , Masculino , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Restrição Física , Taquicardia/etiologia
14.
Brain Res ; 1751: 147195, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33159974

RESUMO

The lateral hypothalamus (LH) is a diencephalic structure that has been considered part of the central circuitry regulating the baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this hypothalamic area are poorly understood. Therefore, in the present study we investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the LH acting via local CRF1 and CRF2 receptors in cardiac baroreflex responses in unanesthetized rats. For this, the baroreflex activity was assessed using two approaches: i) the pharmacological approach via intravenous infusion of vasoactive agents, and ii) the sequence analysis technique that evaluates reflex responses during spontaneous arterial pressure variations. The sequence analysis technique indicated that LH treatment with the selective CRF1 receptor antagonist CP376395 decreased the baroreflex effectiveness index, whereas the selective CRF2 receptor antagonist antisauvagine-30 increased the reflex shortening of pulse interval during spontaneous arterial pressure decreases. However, the pharmacological approach did not indicate effect of the bilateral microinjection of either CP376395 or antisauvagine-30 into the LH in the tachycardia evoked by blood pressure decrease or the reflex bradycardia caused by blood pressure increase. Overall, these findings indicate that CRF neurotransmission within the LH controls baroreflex function during a narrow range of physiological arterial pressure variations. Besides, results provide evidence that CRF1 and CRF2 receptors in the LH oppositely modulate the spontaneous baroreflex activity through different mechanisms.


Assuntos
Barorreflexo/fisiologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Aminopiridinas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicardia , Fármacos Cardiovasculares/farmacologia , Hormônio Liberador da Corticotropina/metabolismo , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Região Hipotalâmica Lateral/metabolismo , Região Hipotalâmica Lateral/fisiologia , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/genética , Transmissão Sináptica/efeitos dos fármacos , Taquicardia
15.
J Psychopharmacol ; 34(4): 429-440, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31913077

RESUMO

BACKGROUND: Endocannabinoid neurotransmission in the bed nucleus of the stria terminalis is involved in the control of cardiovascular responses to stress. However, the local mechanisms involved is this regulation are not known. AIMS: The purpose of this study was to assess an interaction of bed nucleus of the stria terminalis endocannabinoid neurotransmission with local nitrergic signaling, as well as to investigate the involvement of local N-methyl-D-aspartate glutamate receptor and nitric oxide signaling in the control of cardiovascular responses to acute restraint stress by bed nucleus of the stria terminalis endocannabinoid neurotransmission in rats. METHODS: The first protocol evaluated the effect of intra-bed nucleus of the stria terminalis microinjection of the selective cannabinoid receptor type 1 receptor antagonist AM251 in nitrite/nitrate content in the bed nucleus of the stria terminalis following restraint stress. The other protocols evaluated the impact of local pretreatment with the selective N-methyl-D-aspartate glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase inhibitor Nω-propyl-L-arginine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or the protein kinase G inhibitor KT5823 in restraint-evoked cardiovascular changes following bed nucleus of the stria terminalis treatment with AM251. RESULTS: Bilateral microinjection of AM251 into the bed nucleus of the stria terminalis increased local nitric oxide release during restraint stress. Bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist also enhanced the tachycardia caused by restraint stress, but without affecting arterial pressure increase and sympathetic-mediated cutaneous vasoconstriction. The facilitation of restraint-evoked tachycardia following bed nucleus of the stria terminalis treatment with the cannabinoid receptor type 1 receptor antagonist was completely inhibited by local pretreatment with LY235959, Nω-propyl-L-arginine, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, or KT5823. CONCLUSIONS: Our results provide evidence that bed nucleus of the stria terminalis endocannabinoid neurotransmission inhibits local N-methyl-D-aspartate/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling, and this mechanism is involved in the control of the cardiovascular responses to stress.


Assuntos
Hemodinâmica/efeitos dos fármacos , Receptor CB1 de Canabinoide/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Animais , Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de GMP Cíclico/efeitos dos fármacos , Guanilato Ciclase/antagonistas & inibidores , Guanilato Ciclase/efeitos dos fármacos , Masculino , Microinjeções , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/efeitos dos fármacos , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Restrição Física , Transmissão Sináptica/efeitos dos fármacos
16.
Brain Res ; 1710: 109-116, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30605625

RESUMO

The baroreflex is a prominent moment-to-moment mechanism regulating the blood pressure. The hippocampus is a limbic structure in which has been pointed out as part of central network regulating baroreflex. However, the local neurochemical mechanisms involved in control of baroreflex function are not completely understood. Thus, this study aimed to investigate the involvement of nitrergic neurotransmission present in the dorsal hippocampus in baroreflex control of heart rate in conscious rats. For this, we evaluated the effect of bilateral microinjection into the dorsal hippocampus of either the nitric oxide (NO) scavenger carboxy-PTIO, the selective neuronal nitric oxide synthase (nNOS) inhibitor Nω-Propyl-l-arginine (NPLA) or the selective inducible nitric oxide synthase (iNOS) inhibitor 1400 W in bradycardia evoked by blood pressure increases in response to intravenous infusion of phenylephrine, and tachycardia caused by blood pressure decreases evoked by intravenous infusion of sodium nitroprusside. Bilateral microinjection of carboxy-PTIO into the dorsal hippocampus decreased the baroreflex tachycardic response without affecting the reflex bradycardia. Hippocampus treatment with NPLA increased the baroreflex bradycardia gain without affecting the reflex tachycardia. Bilateral hippocampal treatment with 1400 W decreased the reflex tachycardia and increased the baroreflex bradycardic response. Overall, these findings provide evidence that hippocampal nitrergic mechanisms acting in a NOS isoform-specific manner plays a prominent role in control of baroreflex function. Indeed, the results indicate that nNOS and iNOS exerts an inhibitory influence on reflex bradycardia, whereas iNOS mediates the reflex tachycardia.


Assuntos
Barorreflexo/fisiologia , Hipocampo/fisiologia , Óxido Nítrico Sintase Tipo II/fisiologia , Óxido Nítrico Sintase Tipo I/fisiologia , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Ratos Wistar
17.
Eur Neuropsychopharmacol ; 29(5): 672-680, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878320

RESUMO

The lateral hypothalamus (LH) has been described as one of the hypothalamic areas involved in the behavioral and physiological responses triggered by aversive stimuli. Previous studies indicated involvement of the LH in cardiovascular responses to stress. Despite this evidence, the local neurochemical mechanisms involved in LH control of stress responses is still poorly understood. Therefore, in the present study, we investigated the role of GABAergic neurotransmission within the LH in cardiovascular responses induced by an acute session of restraint stress in rats. For this, we evaluated the effect of bilateral microinjection of selective antagonists of either GABAA or GABAB receptors into the LH on arterial pressure increase, heart rate (HR) increase and reduction in tail skin temperature induced by restraint stress. We found that microinjection of the selective GABAA receptor antagonist SR95531 into the LH decreased the increase in HR caused by restraint stress, but without affecting the increase in arterial pressure increase or the reduction in tail skin temperature. Conversely, LH treatment with the selective GABAB receptor antagonist CGP35348 did not affect the restraint-evoked cardiovascular changes. These findings indicate that GABAergic neurotransmission in the LH, acting through activation of local GABAA receptors, plays a facilitatory role in the tachycardic response observed during aversive threats.


Assuntos
Região Hipotalâmica Lateral/metabolismo , Angústia Psicológica , Receptores de GABA-A/metabolismo , Receptores de GABA-B/metabolismo , Estresse Psicológico/metabolismo , Taquicardia/metabolismo , Animais , Antagonistas GABAérgicos/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Região Hipotalâmica Lateral/efeitos dos fármacos , Masculino , Microinjeções , Ratos , Ratos Wistar , Estresse Psicológico/psicologia , Taquicardia/psicologia
18.
Br J Pharmacol ; 175(19): 3773-3783, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30007000

RESUMO

BACKGROUND AND PURPOSE: The aim of the present study was to assess the interaction of nitrergic neurotransmission within the bed nucleus of the stria terminalis (BNST) with local glutamatergic and noradrenergic neurotransmission in the control of cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL APPROACH: Interaction with local noradrenergic neurotransmission was evaluated using local pretreatment with the selective α1 -adrenoceptor antagonist WB4101 before microinjection of the NO donor NOC-9 into the BNST. Interaction with glutamatergic neurotransmission was assessed by pretreating the BNST with a selective inhibitor of neuronal NOS (nNOS), Nω-propyl-L-arginine (NPLA) before local microinjection of NMDA. The effect of intra-BNST NPLA microinjection in animals locally pretreated with WB4101 was also evaluated. KEY RESULTS: NOC-9 reduced the heart rate (HR) and blood pressure increases evoked by restraint stress. These effects of NOC-9 on HR, but not in blood pressure, was inhibited by pretreatment of BNST with WB4101. NMDA enhanced the restraint-evoked HR increase, and this effect was abolished following BNST pretreatment with NPLA. Administration of NPLA to the BNST of animals pretreated locally with WB4101 decreased the HR and blood pressure increases induced by restraint. CONCLUSION AND IMPLICATIONS: These results indicate that inhibitory control of stress-evoked cardiovascular responses by nitrergic signalling in the BNST is mediated by a facilitation of local noradrenergic neurotransmission. The present data also provide evidence of an involvement of local nNOS in facilitatory control of tachycardia during stress by NMDA receptors within the BNST.


Assuntos
Sistema Cardiovascular/metabolismo , Neurônios Nitrérgicos/metabolismo , Núcleos Septais/metabolismo , Estresse Psicológico/metabolismo , Animais , Sistema Cardiovascular/efeitos dos fármacos , Dioxanos/administração & dosagem , Dioxanos/farmacologia , Masculino , Neurônios Nitrérgicos/efeitos dos fármacos , Ratos , Ratos Wistar , Núcleos Septais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Transmissão Sináptica/efeitos dos fármacos
19.
Psychoneuroendocrinology ; 89: 168-176, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29414029

RESUMO

The aims of the present study were to assess an interaction of corticotropin-releasing factor (CRF) neurotransmission within the bed nucleus of the stria terminalis (BNST) with local nitrergic signaling, as well as to investigate an involvement of activation of local NMDA glutamate receptor and nitric oxide (NO) signaling in control of cardiovascular responses to acute restraint stress by BNST CRF neurotransmission in rats. We observed that CRF microinjection into the BNST increased local NO release during restraint stress. Furthermore, bilateral microinjection of CRF into the BNST enhanced both the arterial pressure and heart rate increases evoked by restraint stress, but without affecting the sympathetically-mediated cutaneous vasoconstriction. The facilitation of both pressor and tachycardiac responses to restraint stress evoked by BNST treatment with CRF were completely inhibited by local pretreatment with either the selective NMDA glutamate receptor antagonist LY235959, the selective neuronal nitric oxide synthase (nNOS) inhibitor Nω-Propyl-l-arginine (NPLA), the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the protein kinase G (PKG) inhibitor KT5823. Taken together, these results provide evidence that BNST CRF neurotransmission facilitates local NMDA-mediated glutamatergic neurotransmission and activates nitrergic signaling, and this pathway is involved in control of cardiovascular responses to stress.


Assuntos
Hormônio Liberador da Corticotropina/metabolismo , Miocárdio/metabolismo , Núcleos Septais/metabolismo , Animais , Pressão Sanguínea/fisiologia , Sistema Cardiovascular/metabolismo , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , Coração/fisiologia , Frequência Cardíaca/fisiologia , Masculino , N-Metilaspartato/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Ratos , Ratos Wistar , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Restrição Física/psicologia , Núcleos Septais/fisiologia , Transdução de Sinais , Estresse Psicológico/metabolismo , Transmissão Sináptica/fisiologia
20.
Br J Pharmacol ; 173(19): 2833-44, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27441413

RESUMO

BACKGROUND AND PURPOSE: Endocannabinoid signalling has been reported as an important neurochemical mechanism involved in responses to stress. Previous studies provided evidence of endocannabinoid release in the bed nucleus of the stria terminalis (BNST) during aversive stimuli. Nevertheless, a possible involvement of this neurochemical mechanism in stress responses has never been evaluated. Therefore, in the present study we investigated the involvement of BNST endocannabinoid neurotransmission, acting via local CB1 receptors, in the cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL APPROACH: The selective CB1 receptor antagonist AM251 (1, 30 and 100 pmol 100 nL(-1) ) and/or the fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597 (30 pmol 100 nL(-1) ) or the monoacylglycerol lipase (MAGL) enzyme inhibitor JZL184 (30 pmol 100 nL(-1) ) was microinjected into the BNST before the acute restraint stress. KEY RESULTS: Microinjection of AM251 into the BNST enhanced the tachycardia caused by restraint stress, without affecting the increase in arterial pressure and the sympathetic-mediated cutaneous vasoconstrictor response. Conversely, the increased endogenous levels of AEA in the BNST evoked by local treatment with the FAAH enzyme inhibitor URB597 decreased restraint-evoked tachycardia. Inhibition of the hydrolysis of 2-arachidonoylglycerol (2-AG) in the BNST by local microinjection of the MAGL enzyme inhibitor JZL184 also decreased the HR response. These effects of URB597 and JZL184 were abolished by BNST pretreatment with AM251. CONCLUSIONS AND IMPLICATIONS: These findings indicate an involvement of BNST endocannabinoid neurotransmission, acting via CB1 receptors, in cardiovascular adjustments during emotional stress, which may be mediated by the local release of either AEA or 2-AG.


Assuntos
Sistema Cardiovascular/fisiopatologia , Endocanabinoides/metabolismo , Restrição Física , Núcleos Septais/metabolismo , Estresse Psicológico , Transmissão Sináptica , Doença Aguda , Animais , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Carbamatos/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Núcleos Septais/efeitos dos fármacos , Relação Estrutura-Atividade , Transmissão Sináptica/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA