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Made available in DSpace on 2022-04-28T19:42:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The endocannabinoid neurotransmission acting via local CB1 receptor in the bed nucleus of the stria terminalis (BNST) has been implicated in behavioral and physiological responses to emotional stress. However, the neural network related to this control is poorly understood. In this sense, the lateral hypothalamus (LH) is involved in stress responses, and BNST GABAergic neurons densely innervate this hypothalamic nucleus. However, a role of BNST projections to the LH in physiological responses to stress is unknown. Therefore, using male rats, we investigated the role of LH GABAergic neurotransmission in the regulation of cardiovascular responses to stress by CB1 receptors within the BNST. We observed that microinjection of the selective CB1 receptor antagonist AM251 into the BNST decreased the number of Fos-immunoreactive cells within the LH of rats submitted to acute restraint stress. Treatment of the BNST with AM251 also enhanced restraint-evoked tachycardia. Nevertheless, arterial pressure increase and sympathetically-mediated cutaneous vasoconstriction to restraint was not affected by CB1 receptor antagonism within the BNST. The effect of AM251 in the BNST on restraint-evoked tachycardia was abolished in animals pretreated with the selective GABAA receptor antagonist SR95531 in the LH. These results indicate that regulation of cardiovascular responses to stress by CB1 receptors in the BNST is mediated by GABAergic neurotransmission in the LH. Present data also provide evidence of the BNST endocannabinoid neurotransmission as a mechanism involved in LH neuronal activation during stressful events. Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences Institute of Biological Sciences Federal University of Goiás Laboratory of Pharmacology Department of Department of Drugs and Pharmaceutics School of Pharmaceutical Sciences São Paulo State University - UNESP, Rodovia Araraquara-Jau Km 01 (Campus Universitário), Campus Ville Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences Laboratory of Pharmacology Department of Department of Drugs and Pharmaceutics School of Pharmaceutical Sciences São Paulo State University - UNESP, Rodovia Araraquara-Jau Km 01 (Campus Universitário), Campus Ville FAPESP: 2017/19249-0 FAPESP: 2019/24478-3 CNPq: 304108/2018-9 CNPq: 406393/2018-4 CNPq: 431339/2018-0

S-adenosyl-l-methionine (SAMe), a methyl donor, induces antidepressant effects in preclinical and clinical studies of depression. However, the mechanisms behind these effects have been poorly investigated. Since SAMe is involved in monoamine metabolism, this work aimed at 1) testing the effects induced by systemic treatment with SAMe in mice submitted to the forced swimming test (FST) and tail suspension test (TST); 2) investigating the involvement of serotonergic neurotransmission in the behavioral effects induced by SAMe. To do that, male Swiss mice received systemic injections (1 injection/day, 1 or 7 days) of imipramine (30 mg/kg), L-methionine (400, 800, 1600, and 3200 mg/kg), SAMe (10, 25, 50, 100, and 200 mg/kg), or vehicle (10 ml/kg) and were submitted to the FST or TST, 30 min after the last injection. The effect of SAMe (50 mg/kg) was further investigated in independent groups of male Swiss mice pretreated with p-chlorophenylalanine (PCPA, serotonin synthesis inhibitor, 150 mg/kg daily, 4 days) or with WAY100635 (5-HT

The insular cortex (IC) is engaged in behavioral and physiological responses to emotional stress. Control of physiological functions and behavioral responses has been reported to occur in a site-specific manner along the rostrocaudal axis of the IC. However, a functional topography of the IC regulation of anxiogenic responses caused by stress has never been evaluated. Therefore, we investigated the role of rostrocaudal subregions in the posterior IC in anxiogenic-like effect caused by exposure to acute restraint stress in male rats. For this, rats received bilateral microinjection of the non-selective synaptic inhibitor CoCl

Made available in DSpace on 2021-06-25T10:27:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Inflammation has been described as a prominent mechanism involved in dysfunctions and diseases evoked by chronic stress. Notably, the spleen is an immune organ controlled by sympathetic and glucocorticoid mechanisms, but the impact of chronic stress in the spleen is not entirely understood. Besides, the impact of aerobic exercise training on the effects of chronic stress in the spleen has never been reported. Therefore, this study aimed to assess the changes caused in the spleen by repeated restraint stress and the effect of aerobic exercise training performed after a period of chronic restraint stress in rats. We identified that daily exposure to restraint stress (120 min per session, for 14 consecutive days) increased corticosterone and noradrenaline content, gene expression of glucocorticoid and β2-adrenergic receptors, TNF-α and IL-6 levels, and increased pro-oxidant substances in the spleen. Circulating levels of corticosterone were also increased in chronically stressed animals. Exercise training (1 h a day/5 days per week, for 60 days) increased glucocorticoid receptor gene expression, interleukin (IL)-10 and antioxidant mechanisms in the spleen. Exercise also decreased splenic noradrenaline, tumoral necrosis factor (TNF)-α, and IL-6 contents. Lastly, the effects of repeated restraint stress in the spleen were mitigated in animals subjected to aerobic training. Taken together, the results reported in the present study indicate that aerobic exercise training is a relevant non-pharmacological therapeutic approach to dysfunctions in the spleen caused by a period of stress. Laboratory of Cardiovascular Investigation and Exercise (LICE) School of Physical Education University of Campinas (UNICAMP) Department of Structural and Functional Biology Institute of Biology University of Campinas (UNICAMP) Department of Drugs and Pharmaceutics School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Drugs and Pharmaceutics School of Pharmaceutical Sciences São Paulo State University (UNESP)

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 CRF

Made available in DSpace on 2022-04-28T19:44:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic control, which integrates thermoregulation centers and sympathetic outflow to thermoeffector organs. PVN neurons express the neuronal isoform of nitric oxide synthase (nNOS) whose expression is locally upregulated by physical exercise. Thus, the aim of the present study was to evaluate the role of nNOS in the PVN in the exercise-induced hyperthermia. Seven days after surgery, male Wistar rats received bilateral intra-PVN microinjections of the selective nNOS inhibitor Nw-Propyl-L-Arginine (NPLA) or vehicle (saline) and were submitted to an acute progressive exercise session on a treadmill until fatigue. Abdominal and tail skin temperature (Tabd and Ttail, respectively) were measured, and the threshold (Hthr; °C) and sensitivity (Hsen) for heat dissipation calculated. Performance variables were also collected. During the progressive exercise protocol, all animals displayed an increase in the Tabd. However, compared to vehicle group, the microinjection of NPLA in the PVN attenuated the exercise-induced hyperthermia. There was no difference in Ttail or Hthr between NPLA and control rats. In contrast, Hsen was increased in the NPLA group compared to vehicle. In addition, heat storage was lower in NPLA-treated animals. Despite the temperature differences, inhibition of nNOS in the PVN did not affect running performance on the treadmill. These results suggest that nitrergic signaling within the PVN, under nNOS activation, drives the increase of body temperature, being necessary for the proper thermal regulatory mechanisms during progressive exercise-induced hyperthermia. Department of Physiology and Biophysics Institute of Biological Science Federal University of Minas Gerais (ICB/UFMG) Department of Drugs and Medicine School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Drugs and Medicine School of Pharmaceutical Sciences São Paulo State University (UNESP) CNPq: #403769/2016–7 CNPq: PQ-2 #311516/2020–3

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.

Made available in DSpace on 2022-04-28T19:43:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-12 The prelimbic (PL) and infralimbic (IL) subareas of the medial prefrontal cortex (mPFC) have been implicated in physiological and behavioral responses during aversive threats. The previous studies reported the noradrenaline release within the mPFC during stressful events, and the lesions of catecholaminergic terminals in this cortical structure affected stress-evoked local neuronal activation. Nevertheless, the role of mPFC adrenoceptors on cardiovascular responses during emotional stress is unknown. Thus, we investigated the role of adrenoceptors present within the PL and IL on the increase in both arterial pressure and heart rate (HR) and on the sympathetically mediated cutaneous vasoconstriction evoked by acute restraint stress. For this, bilateral guide cannulas were implanted into either the PL or IL of male rats. All animals were also subjected to catheter implantation into the femoral artery for cardiovascular recording. The increase in both arterial pressure and HR and the decrease in the tail skin temperature as an indirect measurement of sympathetically mediated cutaneous vasoconstriction were recorded during the restraint session. We observed that the microinjection of the selective α2-adrenoceptor antagonist RX821002 into either the PL or IL decreased the pressor response during restraint stress. Treatment of the PL or IL with either the α1-adrenoceptor antagonist WB4101 or the α2-adrenoceptor antagonist reduced the restraint-evoked tachycardia. The drop in the tail skin temperature was decreased by PL treatment with the β-adrenoceptor antagonist propranolol and with the α1- or α2-adrenoceptor antagonists. The α2-adrenoceptor antagonist into the IL also decreased the skin temperature response. Our results suggest that the noradrenergic neurotransmission in both PL and IL mediates the cardiovascular responses to aversive threats. Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint Federal University of São Carlos (UFSCar) - São Paulo State University (UNESP) Graduate Program in Physiological Sciences Institute of Biological Sciences Federal University of Goiás Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint Federal University of São Carlos (UFSCar) - São Paulo State University (UNESP) Graduate Program in Physiological Sciences

Made available in DSpace on 2019-10-06T16:04:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-02 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) School of Medicine We investigated the involvement of nitrergic neurotransmission within the paraventricular nucleus of the hypothalamus (PVN) in modulation of local neuronal activation, autonomic and neuroendocrine responses and behavioral consequences of acute restraint stress in rats. Bilateral microinjections of the selective neuronal nitric oxide (NO) synthase (nNOS) inhibitor N w -Propyl-L-arginine (NPLA) or the NO scavenger carboxy-PTIO into the PVN reduced arterial pressure and heart rate increases, as well as the fall in cutaneous tail temperature induced by restraint stress. PVN injection of either NPLA or carboxy-PTIO also inhibited restraint-induced increases in anxiety-related behaviors in the elevated plus-maze 24 h later. Local microinjection of NPLA or carboxy-PTIO into the PVN reduced the number of c-fos-immunoreactive neurons in the dorsal parvocellular, ventromedial, medial parvocellular and lateral magnocelllular portions of the PVN in animals subjected to restraint stress. However, neither NPLA nor carboxy-PTIO into the PVN affected restraint-induced increases in plasma corticosterone concentration. The present results indicate that PVN nitrergic neurotransmission acting via nNOS activation has a facilitatory influence on autonomic responses to acute restraint and the delayed emotional consequences of restraint stress. Our results also provide evidence of a prominent role of local nitrergic neurotransmission in PVN neuronal activation during stress. Departments of Pharmacology of the School of Medicine of Ribeirão Preto University of São Paulo, 14049-900 Ribeirão Preto Department of Natural Active Principles and Toxicology School of Pharmaceutical Sciences UNESP - São Paulo State University Department of Psychiatry and Behavioral Neuroscience University of Cincinnati Department of Natural Active Principles and Toxicology School of Pharmaceutical Sciences UNESP - São Paulo State University FAPESP: 2009/05308-8 FAPESP: 2012/09425-1 FAPESP: 2013/13721-8 CNPq: 308137/2014-0

Made available in DSpace on 2019-10-06T15:31:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-02 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences CNPq: 305583/2015-8 CNPq: 456405/2014-3

Made available in DSpace on 2021-06-25T11:03:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-16 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) BACKGROUND: Ethanol use is related to a wide variety of negative health outcomes, including cardiovascular diseases. Stress is also involved in numerous pathologies, such as cardiovascular diseases and psychiatric disorders. Sexual dimorphism is an important factor affecting cardiovascular response and has been proposed as a potential risk factor for sex-specific health problems in humans. Here, we evaluated the effect of prolonged ethanol vapor inhalation on arterial pressure, heart rate, and tail skin temperature responses to acute restraint stress, investigating differences between male and female rats. METHODS: We exposed male and female Long-Evans rats to ethanol vapor for 14 h, followed by ethanol withdrawal for 10 h, for 30 consecutive days, or to room air (control groups). The animals underwent surgical implantation of a cannula into the femoral artery for assessment of arterial pressure and heart rate values. The tail skin temperature was measured as an indirect measurement of sympathetic vasomotor response. RESULTS: Chronic ethanol vapor inhalation reduced basal heart rate in both female and male rats. Sex-related difference was observed in the decrease of tail cutaneous temperature evoked by stress, but not in the pressor and tachycardiac responses. Furthermore, prolonged ethanol inhalation enhanced the blood pressure and heart rate increase caused by acute restraint stress in male, but not in female rats. However, no effect of chronic ethanol vapor was observed in the tail cutaneous temperature response to restraint in either sex. CONCLUSION: Chronic ethanol vapor exposure increased the cardiovascular reactivity to stress in male, but not in female rats. Laboratory of Neuropsypharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP), Rod. Araraquara-Jaú km 1 Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís km 235 Laboratory of Pharmacology Paulista Medicine School Universidade Federal de São Paulo - UNIFESP Leal Prado Building, Botucatu 862 StreetVila Clementino Laboratory of Psychology Psychology Department Universidade Federal de São Carlos - UFSCar, Rod. Washington Luís km 235 Joint Graduate Program in Pharmacology Pharmacology and Molecular Biology Institute - INFAR, Três de Maio 100 StreetVila Clementino Biomedical Sciences Institute Universidade Federal de Uberlândia Laboratory of Neuropsypharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP), Rod. Araraquara-Jaú km 1 Joint Graduate Program in Physiological Sciences UFSCar/UNESP, Rod. Washington Luís km 235 CNPq: 164060/2014-6 FAPESP: 2013/24896-2

Made available in DSpace on 2021-06-25T10:12:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The brain renin-angiotensin system (RAS) has been implicated in anxiety and depression disorders, but the specific brain sites involved are poorly understood. The medial amygdaloid nucleus (MeA) is involved in expression of behavioral responses. However, despite evidence of the presence of all angiotensinergic receptors in this amygdaloid nucleus, regulation of anxiety- and depressive-like behaviors by angiotensinergic neurotransmissions within the MeA has never been reported. Thus, the present study aimed to investigate the role angiotensin II (AT1 and AT2 receptors) and angiotensin-(1–7) (Mas receptor) receptors present within the MeA in behavioral responses in the elevated plus-maze (EPM) and forced swimming test (FST). For this, male Wistar rats had cannula-guide bilaterally implanted into the MeA, and independent sets of animals received bilateral microinjections of either the selective AT1 receptor antagonist losartan, the selective AT2 receptor antagonist PD123319, the selective Mas receptor antagonist A-779 or vehicle into the MeA before the EPM and FST. Treatment of the MeA with either PD123319 or A-779 decreased the EPM open arms exploration, while losartan did not affect behavioral responses in this apparatus. However, intra-MeA microinjection of losartan decreased immobility in the FST. Administration of either PD123319 or A-779 into the MeA did not affect the immobility during the FST, but changed the pattern of the active behaviors swimming and climbing. Altogether, these results indicate the presence of different angiotensinergic mechanisms within the MeA controlling behavioral responses in the FST and EPM. School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences FAPESP: 2017/19249-0 CNPq: 431339/2018-0 CNPq: 456405/2014-3

Made available in DSpace on 2022-04-29T08:32:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage. Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Pharmacology School of Medicine of Ribeirão Preto University of São Paulo Department of Adapted Physical Activity Faculty of Physical Education University of Campinas-UNICAMP Department of Physiology School of Medicine of Ribeirão Preto University of São Paulo Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)

Made available in DSpace on 2021-06-25T11:12:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Clonidine (CL) and Rilmenidine (RI) are among the most frequently prescribed centrally acting antihypertensives. Here, we compared CL and RI effects on psychogenic cardiovascular reactivity to sonant, luminous, motosensory, and vibrotactile stimuli during neurogenic hypertension. The femoral artery and vein of Wistar (WT – normotensive) and spontaneously hypertensive rats (SHR) were catheterized before (24 h interval) i.p. injection of vehicle (NaCl 0.9%, control - CT group), CL (10 µg/kg), or RI (10 µg/kg) and acute exposure to luminous (5000 lm), sonant (75 dB sudden tap), motor (180° cage twist), and air-jet (10 L/min – restraint and vibrotactile). Findings showed that: (i) CL or RI reduced the arterial pressure of SHR, without affecting basal heart rate in WT and SHR; (ii) different stimuli evoked pressor and tachycardic responses; (iii) CL and RI reduced pressor response to sound; (iv) CL or RI reduced pressor responses to luminous stimulus without a change in peak tachycardia in SHR; (v) cage twist increased blood pressure in SHR, which was attenuated by CL or RI; (vi) air-jet increased pressure and heart rate; (vii) CL or RI attenuated the pressor responses to air-jet in SHR while RI reduced the chronotropic reactivity in both strains. Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air-jet-induced tachycardia. Institute of Biological Sciences Federal University of Goias School of Medicine Federal University of Goias Institute of Biomedical Sciences Federal University of Uberlandia Institute of Biological Sciences Federal University of Minas Gerais School of Dentistry São Paulo State University (UNESP) School of Pharmaceutical Sciences São Paulo State University (UNESP) School of Dentistry São Paulo State University (UNESP) School of Pharmaceutical Sciences São Paulo State University (UNESP)

Made available in DSpace on 2021-06-25T11:14:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 The aim of this study was to investigate the effect of rosuvastatin treatment on memory impairment, and anxiogenic-like effects in mice chronically infected with Toxoplasma gondii. For this, Balb/c mice were infected orally with chronic ME-49 strain of Toxoplasma gondii. Oral treatment with rosuvastatin (40mg/kg/day) started on the 51st day post-infection and was performed daily for 21 days. After completion of treatment, anxiety-like effects and locomotion were investigated in the open field (OF) test, whereas novel object recognition (NOR) test was used for evaluation of short- and long-term memory. At the end of the experiments, the brain was collected for Toxoplasma gondii DNA quantification and histopathological analysis. Infection with ME-49 strain decreased the time spent in the center of OF, indicating an anxiogenic effect, without affecting total and peripheral locomotion. Rosuvastatin treatment inhibited the change in the center time. Besides, pharmacological treatment increased total and central locomotion in both non-infected and infected animals. Infection also impaired both short- and long-term memory in the NOR test, and these effects were reverted by rosuvastatin treatment. In addition to effects in behavioral changes, rosuvastatin also reduced parasite load in the brain and attenuated signs of brain inflammation such as perivascular cuffs, inflammatory cell infiltration and tissue damage. These findings indicate for the first time the efficacy of rosuvastatin in treatment of memory impairment and anxiogenic effect evoked by infection with Toxoplasma gondii. These effects might be mediated by reduced cyst load, which in turn decrease inflammation and damage in the brain. Health Sciences Department State University of Maringá (UEM) School ofPharmaceutical Sciences São Paulo State University (UNESP) PharmaceuticalSciences Program State University of Maringá (UEM) Resident of Obstetric Nursingof the Municipal Health Authority of Apucarana School ofPharmaceutical Sciences São Paulo State University (UNESP)

The endocannabinoid system is implicated in anxiety, but the brain sites involved are not completely understood. The bed nucleus of the stria terminalis (BNST) has been related to anxiety and responses to aversive threats. Besides, endocannabinoid neurotransmission acting via CB

Background: Ethanol use is related to a wide variety of negative health outcomes, including cardiovascular diseases. Stress is also involved in numerous pathologies such as cardiovascular diseases and psychiatric disorders. Sexual dimorphism is an important factor affecting the cardiovascular response and have been proposed as a potentially risk factor for sex-specific health problems in human. Here, we evaluated the effect of prolonged ethanol vapor inhalation in arterial pressure, heart rate and tail skin temperature responses to acute restraint stress, investigating differences between male and female rats. Methods: We exposed male and female Long-Evans rats to ethanol vapor for 14 hours, followed by ethanol withdrawal for 10 hours, for 30 consecutive days or room air (control groups). The animals underwent surgical implantation of a cannula into the femoral artery for assessment of arterial pressure and heart rate values. The tail skin temperature was measured as an indirect measurement of sympathetic vasomotor response. Results: Chronic ethanol vapor inhalation reduced basal heart rate in both female and male rats. Sex-related difference was observed in the decrease of tail cutaneous temperature evoked by stress, but not in the pressor and tachycardiac responses. Furthermore, prolonged ethanol inhalation enhanced the blood pressure and heart rate increase caused by acute restraint stress in male, but not in female rats. However, no effect of chronic ethanol vapor was observed in the tail cutaneous temperature response to restraint in both sexes. Conclusion: Chronic ethanol vapor exposure increased the cardiovascular reactivity to stress in male, but not in female rats.

Made available in DSpace on 2021-06-25T10:18:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Laboratory of Pharmacology São Paulo State University (UNESP) School of Pharmaceutical Sciences Joint UFSCar-UNESP Graduate Program in Physiological Sciences Laboratory of Pharmacology São Paulo State University (UNESP) School of Pharmaceutical Sciences Joint UFSCar-UNESP Graduate Program in Physiological Sciences FAPESP: 2017/19249-0 CNPq: 431339/2018-0

Made available in DSpace on 2020-12-12T01:33:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-15 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) 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. Department of Pharmacology School of Medicine of Ribeirão Preto University of São Paulo Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Health Sciences Faculty of Medicine – Federal University of Lavras Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) CNPq: 141992/2016-6 FAPESP: 2015/05922-9 CNPq: 456405/2014-3 FAPEMIG: APQ-01316-16

Made available in DSpace on 2020-12-12T01:23:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Laboratory of Pharmacology Saõ Paulo State University (UNESP) School of Pharmaceutical Sciences Joint UFSCarUNESP Graduate Program in Physiological Sciences Department of Adapted Physical Activity Faculty of Physical Education University of Campinas - UNICAMP Laboratory of Pharmacology Saõ Paulo State University (UNESP) School of Pharmaceutical Sciences Joint UFSCarUNESP Graduate Program in Physiological Sciences FAPESP: 2015/05922-9 FAPESP: 2017/19249-0 CNPq: 456405/2014-3

Made available in DSpace on 2020-12-12T01:35:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Department of Drugs and Pharmaceutics Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara KM 01 (Campus Universitário) Joint UFSCar-UNESP Graduate Program in Physiological Sciences Department of Drugs and Pharmaceutics Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara KM 01 (Campus Universitário) Joint UFSCar-UNESP Graduate Program in Physiological Sciences FAPESP: 2015/05922-9 FAPESP: 2017/19249-0 CNPq: 304108/2018-9 CNPq: 305583/2015-8

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 CRF

Made available in DSpace on 2020-12-12T02:45:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 This study aimed to evaluate the impact of aerobic training (AT) on autonomic, cardiometabolic, ubiquitin-proteasome activity, and inflammatory changes evoked by myocardial infarction (MI) in ovariectomized rats. Female Wistar rats were ovariectomized and divided into four groups: sedentary + sham (SS), sedentary + MI (SI), AT + sham surgery (TS), AT + MI (TI). AT was performed on a treadmill for 8 weeks before MI. Infarcted rats previously subjected to AT presented improved physical capacity, increased interleukin-10, and decreased pro-inflammatory cytokines. Metabolomic analysis identified and quantified 62 metabolites, 9 were considered significant by the Vip Score. SS, SI, and TS groups presented distinct metabolic profiles; however, TI could not be distinguished from the SS group. MI dramatically increased levels of dimethylamine, and AT prevented this response. Our findings suggest that AT may be useful in preventing the negative changes in functional, inflammatory, and metabolic parameters related to MI in ovariectomized rats. Department of Structural and Functional Biology Institute of Biology University of Campinas (UNICAMP) Department of Bioscience Federal University of São Paulo (UNIFESP) Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Department of Physical Education Federal University of Maranhão (UFMA) School of Physical Education and Sport University of São Paulo Department of Cancer Physiology H. Lee Moffitt Cancer Center and Research Institute Department of Adapted Physical Activity School of Physical Education University of Campinas (UNICAMP) Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP)

Made available in DSpace on 2020-12-12T01:11:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 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. Laboratory of Pharmacology São Paulo State University (UNESP) School of Pharmaceutical Sciences Joint Federal University of São Carlos (UFSCar) UNESP Graduate Program in Physiological Sciences Laboratory of Pharmacology São Paulo State University (UNESP) School of Pharmaceutical Sciences Joint Federal University of São Carlos (UFSCar) UNESP Graduate Program in Physiological Sciences

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.

Made available in DSpace on 2018-12-11T17:20:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-07-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Studies showed that physical exercise decreases the risk of developing Parkinson's disease (PD) as slowing its progression. Nitric oxide (NO) increases in the substantia nigra pars compacta (SNpc) of individuals with PD. However, no study has evaluated the effects of exercise on peripheral NO levels and its modulatory effects on cardiovascular dysfunctions of subjects with PD. Trained (T) or sedentary (S) animals underwent stereotactic surgery for bilateral 6-hydroxydopamine (6-OHDA) or vehicle microinfusion (Sham group). After 6 days, the animals were catheterized for baseline parameters, followed by inhibition of NOS by Nw-nitro-arginine-methyl ester (L-NAME, 10 mg/kg - i.v.). Nitrite concentration was performed in the aorta, heart, kidney, adrenal and plasma. After exercise, the animals presented resting bradycardia (6-OHDA T and Sham T). NO was increased in the aorta of 6-OHDA S, and decreased in 6-OHDA T animals. In the heart, NO was increased in Sham T compared to sedentary and decreased in 6-OHDA T relative to 6-OHDA S and Sham T animals. At the kidney, NO decrease in 6-OHDA S and Sham T when compared to Sham S and, in adrenal gland, there was a decrease in 6-OHDA T in relation to 6-OHDA S. L-NAME promoted lower increases in MAP in 6-OHDA groups. The decreases of HR were enhanced due to physical training. 6-OHDA S group presented decreased systolic arterial pressure variability, not altered by exercise. Our data showed alterations in peripheral NO in the association of exercise with Parkinsonism in the cardiovascular function. Departamento de Ciências Fisiológicas Universidade Estadual de Londrina – UEL Faculdade de Ciências Farmacêuticas de Araraquara Departamento de Princípios Ativos Naturais e Toxicologia Universidade Estadual Paulista – UNESP Departamento de Ciências Patológicas Universidade Estadual de Londrina – UEL Faculdade de Ciências Farmacêuticas de Araraquara Departamento de Princípios Ativos Naturais e Toxicologia Universidade Estadual Paulista – UNESP CAPES: 1583617

Made available in DSpace on 2021-06-25T10:23:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-30 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The endocannabinoid system is implicated in anxiety, but the brain sites involved are not completely understood. The bed nucleus of the stria terminalis (BNST) has been related to anxiety and responses to aversive threats. Besides, endocannabinoid neurotransmission acting via CB1 receptors was identified in the BNST. However, the presence of CB2 receptors and the role of BNST endocannabinoid system in anxiety-like behaviors have never been reported. Therefore, this study investigated the presence of CB1 and CB2 receptors in the BNST and their role in anxiety-like behaviors. For this, gene expression of the endocannabinoid receptors was evaluated in samples from anterior and posterior BNST. Besides, behaviors were evaluated in the elevated plus-maze (EPM) in unstressed rats (trait anxiety-like behavior) and after exposure to restraint stress (restraint-evoked anxiety-like behavior) in rats treated with either the CB1 receptor antagonist AM251 or the CB2 receptor antagonist JTE907 into the anterior BNST. The presence of CB1 and CB2 receptors gene expression was identified in anterior and posterior divisions of the BNST. Bilateral microinjection of AM251 into the anterior BNST dose-dependently increased EPM open arms exploration in unstressed animals and inhibited the anxiety-like behavior in the EPM evoked by restraint. Conversely, intra-BNST microinjection of JTE907 decreased EPM open arms exploration in a dose-dependent manner and inhibited restraint-evoked behavioral changes in the EPM. Taken together, these results indicate that CB1 and CB2 receptors present in the BNST are involved in control of anxiety-like behaviors, and control by the latter is affected by previous stress experience. Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences Department of Pharmacology Paulista Medicine School São Paulo Federal University Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences FAPESP: 2017/19249-0

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.

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. Adolescence has been proposed as a developmental period of vulnerability to stress. This idea has been mainly supported by experimental research in animals demonstrating a higher impact of chronic emotional stress in adolescents compared with adults. Adolescent vulnerability is also based on evidence that stress during this developmental period affects development, so that enduring changes are found in adult animals that experienced stress during adolescence. The purpose of the present review is to discuss experimental research in rodent models that investigated the impact of long-term exposure to stressful events during adolescence on cardiovascular function. The development of cardiovascular function and autonomic activity in rodents is initially reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular effects of chronic stress is presented. From the reviewed literature, perspective for future research is proposed to better elucidate adolescent vulnerability to cardiovascular complications evoked by chronic emotional stress.

Made available in DSpace on 2019-10-06T15:51:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The medial amygdaloid nucleus (MeA) is a limbic structure that has been demonstrated to be part of the central circuitry regulating baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this forebrain structure is poorly understood. Thus, in the present study, we investigated the specific role of AT1, AT2, and MAS angiotensinergic receptors within the MeA in baroreflex responses in unanesthetized rats. For this, the baroreflex function was assessed using both the pharmacological approach via intravenous infusion of vasoactive agents and the sequence analysis technique. Using the pharmacological approach, we observed that bilateral microinjection of the selective AT2 receptor antagonist PD123319 into the MeA increased the tachycardia evoked by blood pressure decrease, but without affecting the reflex bradycardia caused by blood pressure increase. Besides, bilateral microinjection of the selective MAS receptor antagonist A-779 decreased both tachycardic and bradycardic responses of the baroreflex. The sequence analysis technique indicated that PD123319 into the MeA increased baroreflex effectiveness index while A-779 had an opposite effect. Treatment of the MeA with the selective AT1 receptor antagonist losartan did not affect baroreflex function assessed by either the pharmacological approach or sequence analysis technique. Overall, these findings provide evidence that MAS receptor within the MeA plays a facilitatory role in baroreflex function, whereas local AT2 receptor inhibits cardiac baroreflex responses. Results also indicate that AT1 receptor within the MeA is not involved in the control of baroreflex function. Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara-Jaú Km 01 (Campus Universitário), Campus Ville Joint UFSCar-UNESP Graduate Program in Physiological Sciences Laboratory of Pharmacology School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara-Jaú Km 01 (Campus Universitário), Campus Ville Joint UFSCar-UNESP Graduate Program in Physiological Sciences FAPESP: 2015/05922-9 FAPESP: 2017/19249-0 CNPq: 304108/2018-9 CNPq: 456405/2014-3

Made available in DSpace on 2020-12-12T01:05:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Universidade Estadual Paulista 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. São Paulo State University (UNESP) School of Pharmaceutical Sciences Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos São Paulo State University (UNESP) School of Pharmaceutical Sciences Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos CNPq: 141992/2016-6 FAPESP: 2015/05922-9 FAPESP: 2017/19249-0 Universidade Estadual Paulista: 304108/2018-9 Universidade Estadual Paulista: 305583/2015-8 CNPq: 456405/2014-3

Made available in DSpace on 2019-10-06T15:50:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 The present study investigated the effect of the treatment with the angiotensin II type 1 receptor (AT1) antagonist losartan in the depressive-like state and memory impairment evoked by exposure to either homotypic (i.e., repeated exposure to the same type of stressor) or heterotypic (i.e., exposure to different aversive stimuli) chronic stressors in rats. For this, male Wistar rats were subjected to a 10 days regimen of repeated restraint stress (RRS, homotypic stressor) or chronic variable stress (CVS, heterotypic stressor) while being concurrently treated daily with losartan (30 mg/kg/day, p.o.). Depressive-like state was evaluated by analysis of the alterations considered as markers of depression (decreased sucrose preference and body weight and coat state deterioration), whereas cognitive non-emotional performance was tested using the novel object recognition (NOR) test. Locomotor activity was also evaluated in the open field test. Both RRS and CVS impaired sucrose preference and caused coat state deterioration, whereas only CVS impaired body weight gain. Besides, RRS impaired short-term memory (but not long-term memory) in the NOR test. Neither depressive-like state nor memory impairment evoked by the chronic stressors was affected by the treatment with losartan. Nevertheless, CVS increased the locomotion, which was inhibited by losartan. Taken together, these results provide evidence that the chronic treatment with losartan does not affect the depressive-like state and memory impairment evoked by either homotypic or heterotypic chronic stress regimens in rats. School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP) Joint UFSCar-UNESP Graduate Program in Physiological Sciences

The medial amygdaloid nucleus (MeA) is a limbic structure that has been demonstrated to be part of the central circuitry regulating baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this forebrain structure is poorly understood. Thus, in the present study, we investigated the specific role of AT