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Item Efeitos do treinamento físico aeróbico sobre as respostas cardiovasculares e autonômicas induzidas pela estimulação do processo neuroinflamatório em ratos espontaneamente hipertensos: enfoque no núcleo paraventricular hipotalâmico(Universidade Federal de Goiás, 2023-07-26) Dias, Matheus Lobo Perez; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Pedrino, Gustavo Rodrigues; Rosa, Daniel Alves; Pansani, Aline PriscilaThe autonomic nervous system (ANS) comprises the sympathetic nervous system (SNS) and the parasympathetic nervous system (PSNS), which are associated with the regulation of the cardiovascular function. Neuroinflammation and the increase of the sympathetic tone are reported as angular stone in the genesis of the arterial hypertension (AH), which is the main factor for modifiable risk for the problem associated with development, maintenance and aggravation in the cardiovascular diseases (CVD). The sympathetic flow is modulated by different elemental nucleus located in the central nervous system (CNS), such as the hypothalamic paraventricular nucleus (PVN) and the rostral ventrolateral medulla (RVLM). Conditions circumscribed to these regions are frequently implicated to the autonomic imbalance, driving force in pathogenesis of the AH. Although the neurons in these cardiovascular and autonomic central control regions contribute to the modulation of the sympathetic flow, the factors that cooperate to the increase of the neuron activity are still under investigation. In the last decades, many experimental evidence related the brain cytokines to the autonomic imbalance observed in different models of AH. The tumor necrosis factor alpha (TNFα) is a constituent of the pro-inflammatory cytokines (PICs) that acts as neuromodulator and perform a fundamental role in the sympathetic regulation of the blood pressure (BP). Studies suggest that the increase of the PICs expression activates many signaling ways and acutely influence the neural discharge, promoting adaptative changes that modulate the neuronal excitability through genic transcription. On the other hand, the aerobic physical training (APT) is recognized as a preventive and adjuvant therapeutic too in AH management. In light of these considerations, the present study evaluated the contribution of the neuroinflammatory process to the cardiovascular and autonomic responses induced by TNF-α in the PVN of hypertensive animals undergoing a regular moderate-intensity APT protocol. To this end, SHR (250 - 350g) were divided into two groups: I. SHR-APT (8 weeks of aerobic training, n=13); II. SHR-SED (8 weeks of supervision in species-typical physical activity, n=10). The systolic blood pressure (SBP) and the heart rate (HR) was monitored throughout the whole treatment period with the tail plethysmography (TP). At the end of the 8 weeks, the animals were anesthetized with urethane (400 mg·kg−1 body weight; i.v.) associated with α-chloralose (40 mg·kg−1 body weight; i.v.) and surgically instrumented for unilateral intranuclear nanoinjections (50nL) in the PVN, recording of mean arterial XX pressure (MAP), HR and splanchnic sympathetic nerve activity (SSNA). During the non-anesthetized records, we identified that the APT promoted resting bradycardia observed from the 3rd week of training (SHR-APT: from 488,9 ± 13,1 to 450,2 ± 11,6 bpm; p<0,05). In the fraction of the study where the recordings were performed in anesthetized SHR, we identified that the vehicle nanoinjections (phosphate-buffered saline; PBS, 0.01 M) in the PVN didn’t promote the change in the basal values of the MAP (SHR-SED: Δ -2,1 ± 1,3; SHR-APT: Δ -0,7 ± 1,4 mmHg; 10 min after vehicle, from baseline), HR (SHR-SED: Δ 0,039 ± 1,6; SHR-APT: Δ -1,0 ± 1,8 bpm; 10 min after vehicle, from baseline) and ∫SSNA (SHR-SED: Δ +9,7 ± 2,0; SHR-APT: Δ +4,3 ± 1,7%; 10 min after vehicle, from baseline), in the same way that it wasn’t observed differences between the groups. In the other hand, intranuclear nanoinjections of TNFα in the PVN of hypertensive animals that remained in species-typical physical activity induced an increase in MAP (SHR-SED: Δ +11,4 ± 3,9 mmHg; p<0,05; 50 min after TNF-α, from baseline), HR (SHR-SED: Δ +18.8 ± 4.5 bpm; p<0.05; 60 min after TNFα, from baseline) and ∫SSNA (SHR-SED: Δ +21.8 ± 4.7 %; p<0.05, 20 min after TNFα, from baseline). In SHR submitted to APT, we found that nanoinjections of TNF-α into the PVN did not elicit pressor responses (SHR-TFA: Δ -4.6 ± 2.4 vs. SHR-SED: Δ +6.8 ± 4.2 mmHg; p<0.05; 40 min after TNF-α), nor did they result in sympathetic excitation (SHR-SED: Δ +30.6 ± 4.7 vs. SHR-TFA: Δ +14.3 ± 4.9 %; p<0.05; 30 min after TNF-α), as observed in the sedentary group. Additionally, there was a significant difference in these parameters when comparing the training groups to the sedentary groups of animals. Taken together, our findings demonstrate that regularly performed moderate-intensity APT effectively promotes resting bradycardia while also mitigating the increase in SSNA and pressor response induced by acute activation of the neuroinflammatory process in the PVN of SHR.Item Contribuição dos receptores de grelina dos neurônios pré-motores simpáticos do hipotálamo paraventricular para o controle da função cardiovascular(Universidade Federal de Goiás, 2018-05-09) Santana, Joice Simões; Custódio, Carlos Henrique Xavier; http://lattes.cnpq.br/0207928273284808; Ferreira, Reginaldo Nassar; http://lattes.cnpq.br/2555785079833283; Ferreira, Reginaldo Nassar; Custódio, Carlos Henrique Xavier; Ferreira, Patrícia Maria; Colugnati, Diego Basileon the balance of the excitatory and inhibitory synapses, such as gabaergic ones, is responsible for cardiovascular system modulation. The effects of ghrelin, a 28-amino acids peptide, are mediated by subtype 1a of the growth hormone secretagogue receptor (GHSR1a), densely expressed in the sympathetic pre-motor neurons of PVH. Therefore, this work investigated the effects of ghrelin on the control exercised by PVH on cardiovascular system and its relationship with gabaergic activity. For this purpose, mean systemic arterial pressure (PAM) in the femoral artery and pressure in the left cardiac ventricle (LVP) of Wistar rats (250-300 g) were measured by catheterization. Treatment with 100 nL of 0.03 nM ghrelin injected directly into PVH reduced PAM by 40 ± 12 mmHg and the maximum blood pressure in the left cardiac ventricle (LVPmax) by 28 ± 12 mmHg, as well as its derivative as a function of time (LVdP / dTmax), a measure of inotropism, which was reduced by 2051 ± 946 mmHg / s, without causing statistically significant changes in cardiac chronotropism. In contrast, to demonstrate that the effects of ghrelin were mediated by GHS-R1a, the inhibition of this receptor with 100 nL of PF04628935 (0.06 nM) in PVH caused an increase in PAM of 8 ± 3 mmHg and of LVPmax by 29 ± 8 mmHg; in addition to stimulating inotropism, with LVdP / dTmax being elevated at 1449 ± 467 mmHg / s, and chronotropism, with elevated heart rate at 29 ± 12 bpm. Finally, the comparison of its effects with muscimol, a GABAA receptor agonist, demonstrated that ghrelin potentiated the reduction in blood pressure induced by that drug, reducing PAM by 19 ± 5 mmHg, without significantly altering the pressure in the cardiac left ventricle and inotropism. Interestingly, ghrelin promoted na increase in heart rate by 27 ± 12 bpm, after muscimol injection. The present study demonstrated that the ghrelin axis - GHS-R1a in PVH contributes to cardiovascular control and related these effects to interactions with the gabaergic system.Item Efeito do extrato líquido concentrado obtido dos resíduos agroindustriais dos frutos de Myrciaria cauliflora sobre parâmetros cardiometabólicos de ratos Wistar submetidos ao modelo de obesidade induzida por glutamato monossódico(Universidade Federal de Goiás, 2020-02-13) Teófilo , Monatha Nayara Guimarães T; Blanch, Graziela Torres; http://lattes.cnpq.br/8106735874828106; Oliveira , André Henrique Freiria; http://lattes.cnpq.br/0152151142555605; Oliveira , André Henrique Freiria; Rosa, Daniel Alves; Fajemiroye, James OluwagbamigbeObesity is a multifactorial disease that develops from an imbalance in the energy balance (EB). The lesion in the arcuate nucleus of the hypothalamus in rodents causes an imbalance in EB, biochemical and hormonal resulting in excess body fat storage in the body. The concentrated liquid extract of the residue of the fruit of the jabuticaba - Myrciaria cauliflora (ECJ) has become promising in the prevention/ treatment of chronic diseases, such as obesity, due to its bioactive compounds and antioxidant properties. The purpose of this work was to analyze the effects of ECJ (3%) on body mass, blood pressure, hematological and biochemical parameters in obese rats with monosodium glutamate (MSG). In the first days of life, the rats received subcutaneous injections in the posterior cervical region of MSG (4 mg/g) and control rats injected with isotonic saline (0.9%). After the weaning period (21 days), the animals were distributed in 4 experimental groups, treated or not for 60 days with the ECJ (3%) by gavage, group 1: control (CT); group 2: control treated with the extract (CT+E); group 3: monosodium glutamate (MSG); group 4: monosodium glutamate treated with the extract (MSG+E). In our study, rats that received injections of MSG with or without ECJ (3%) had: lower body weight gain and nasal/anal length, higher Lee index, and fat weight: retroperitoneal, inguinal and epididymal, lower cardiac index, lower liver and kidney weight, and lymphocytopenia. The rats that received only MSG showed an increase in mean blood pressure (MAP), increased levels of triglycerides (TG), and very-low-density lipoprotein (VLDL), leukopenia, the relative increase in monocytes, eosinophils and basophils. The MSG+E group demonstrated values of MAP, TG, VLDL, and leukocytes similar to those of animals CT+E and a lower level of low-density lipoprotein (LDL). There were no significant histological differences in cardiac tissue, total cholesterol, high-density lipoprotein, and in levels of tumor necrosis factor-alpha, interleukin 6, interleukin 4 and interleukin 10, in animals. From this, we concluded that the MSG was effective in inducing the obesity model and that the treatment with ECJ (3%) for 60 days demonstrated a beneficial protective action through PAM, TG, VLDL, and LDL altered by obesity.Item Controle hidroeletrolítico e respostas cardiovasculares à injeção central de angII, carbacol e hiperosmolaridade plasmática em ratos com epilepsia induzida por pilocarpina(Universidade Federal de Goiás, 2019-11-29) Mercês, Thais Machado das; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Oliveira, André Henrique Freiria de; http://lattes.cnpq.br/0152151142555605; Almeida, Roberto Lopes de; Mendes, Elizabeth Pereira; Oliveira, André Henrique Freiria deStatus epilepticus (SE) is a condition caused by failure of the mechanisms responsible for the termination of the seizure or the onset of the mechanism leading to abnormally prolonged seizures. An epileptic seizure is defined as “the transient occurrence of signs and/or secondary symptoms of abnormal brain neuronal activity”. Epilepsy is a brain syndrome defined by at least one of the following conditions: (1) less than 2 unprovoked epileptic seizures within 24 hours; (2) an unprovoked seizure in individuals who have factors associated with a higher likelihood of having a decreased epileptic threshold; (3) diagnosis of epilepsy syndrome. Individuals with epilepsy are more likely to suffer sudden death, with sudden and unexpected death in epilepsy (SUDEP) a more common category. The pilocarpine-induced epilepsy (PIE) model was the most used to study temporal lobe epilepsy (TLE). The renin angiotensin system (RAS) is known to be involved in some neurodegenerative diseases as well as epilepsy. And, it has been shown that the central nervous system (CNS) areas are responsible for thirst behavior and appetite for waste affected by the epilepsy model. Thus, this study aimed to study cardiovascular control in the face of changes in central levels of angiotensin II (Ang II), carbachol and plasma osmolarity in the PIE model. We used Wistar rats (250-280 g), preused with methylscopolamine (1mg / kg intraperitoneal -ip), after receiving a pilocarpine injection (350 mg / kg-ip) to induce SE. After 3 hours of SE, dizepam (10 mg / kg -i.p.) was injected to stop a seizure. Daily intake of water and 1,8% NaCl, no difference between groups, and body weight were made in which epilepsy group uses a lower weight gain when using a control group (358 ± 13 vs. 406 ± 6 g, respectively). Animals prepared with cannulae directed to the lateral ventricle (VL) were divided into two groups with which cardiovascular records were recorded: one group that removes intracerebroventricular (icv) injection from Ang II and the other one with carbachol. We observed that the pressor response was higher in the epilepsy group when compared to the control after Ang II injection (Epilepsy: 28,0 ± 3,3 vs. Control: 13,3 ± 0,7 mmHg, p <0,05). , a variation in heart rate (ΔHR) was not different between groups. In animals receiving icv carbacol injection, the response was not different between groups, but there was a difference between groups compared with baseline (-0,5 ± 1,4 vs. 22,3 ± 4,6 mmHg, epilepsy and 1,0 ± 2,3 vs. 24,3 ± 4,0 mmHg, control, p <0,05), ΔHR was different between groups (Epilepsy: -24,3 ± 6,1 vs. Control: - 56,3 ± 13,2 bpm), as well as within the control group, comparing their baseline period to the post-carbachol injection period (396,7 ± 17,0 vs. -56,3 ± 13,2 bpm, respectively). In another experiment, the animals were recorded after an intrinsic 12% NaCl overload, which showed a pressure drop at 30, 40 and 50 min in the epilepsy group when compared to 10 minutes after gavage ( 10 ': 5,6 ± 2,9 vs. 30': -8,0 ± 5,3 mmHg; 40 ': -11,5 ± 4,9 mmHg; 50': -9,0 ± 4,5 mmHg ). This was not observed in control animals. Regarding HR there was no difference between the groups, but no group with epilepsy increased after gavage when comparing the times -10, -1, 40, 50 and 60 minutes (10 ': 49,2 ± 23,0 vs. -10 ': 0,0 ± 0,0 bpm; -1': -5,7 ± 11,1 bpm; 40 ': 3,5 ± 7,3 bpm; 50': -7,0 ± 9,6 bpm and 60 ': -5,7 ± 11,3 bpm). Our results suggest that pilocarpine-induced epilepsy is capable of altering angiotensin, carbachol-dependent mechanisms and increased plasma osmolarity, which alter or control harmful blood pressure or corrective substance use and contribute to SUDEP.Item Caracterização das alterações hemodinâmicas ocasionadas pelo reflexo pressórico ao exercício em ratos normotensos e hipertensos: participação do RVLM e possíveis mecanismos periféricos(Universidade Federal de Goiás, 2019-06-28) Silveira, Laíla Milhomem; Rosa, Daniel Alves; http://lattes.cnpq.br/5848020104921718; Rosa, Daniel Alves; Mendes, Elizabeth Pereira; Ferreira Neto, Marcos LuizStatic muscle contraction promotes an increase in blood pressure (BP) and heart rate (HR) by means of a peripheral neural reflex of muscular origin, the " exercise reflex pressure" (EPR). It is well established in the literature that cardiovascular adjustments in responses to physical exercise are altered in hypertensive individuals, and some of these alterations are attributed to the central mechanisms - associated with mismatches in the autonomic sympathetic component - as well as the peripheral mechanisms characterized by vascular endothelial dysfunction. The rostralventrolateral region of the medulla (RVLM) is the main efferent arm of vasomotor neurons for tonic maintenance and BP reflex. Experimental evidence indicates the participation of RVLM in HR and BP increase induced by EPR. However, little is known about its participation in this reflex, regarding hemodynamic adjustments, such as alteration in blood flow (BF) and aortic (AVC) and renal vascular conductance (RVC), of normotensive and hypertensive animals. Objective: investigate the central role of RVLM and peripheral vasodilator mechanisms in hemodynamic changes resulting from EPRevocated by the static muscle contraction of the sural triceps by tibial nerve electrical stimulation (TNES) in WISTAR and spontaneously hypertensive rats(SHR). Methodology: Wistars (n = 10) and SHR (n = 6) (250-350g) were anesthetized and instrumented to record BP, HR, ABF, RBF, AVC and RVC. The left sural triceps tendon was attached to a force transducer to measure the developed muscle tension. The tibial nerve was stimulated by electrical current for 30 s at a frequency of 40Hz, 0.1 ms pulse duration and 5x motor threshold. The TNES was performed before and after quinurenic acid nanoinjection (KYN, 50 nL) in the contralateral RVLM to the stimulated nerv. The injection site was targed, and its medulla was removed for histological analysis. In a later protocol, SHRs (treated SHR, n = 7) were treated with Nebivolol Hydrochloride (NBL, 10mg / kg) or distilled water (control SHR, n = 5) for 15 days by gavage. They were then submitted to the same experimental procedures as the initial protocol, except for the central nanoinjection. Data were expressed as mean +/- SEM and Student's t-test and One-way ANOVA tests were used. P ≤ 0.05.RESULTS: In WISTARs and SHRs, EPR evocated byTNES increased BP and HR, which were reduced after KYNnanoinjection in RVML. In WISTARs, EPR caused increase in ABF and AVC, IX butafter the injection in the contralateral RVLM, we noticed a reduction in this response. In SHR, there were no changes of ABF or AVC during contractions, before and after glutamatergic blockade. In WISTAR animals, EPR produced RBF and RVC reduction during TNES. After the glutamatergic blockade in RVLM, however, the RBF and RVC responses were not altered. The EPR in SHR did not trigger RBF and RVC reduction, as well KYN in RVLM. The 15-day NBL treatment did not alter the SHRs AVC and RVC changes. CONCLUSION: BP and HR responses induced by TNES were reduced with glutamatergic blockade in RVLM in WISTARs and SHRs. In WISTARs, TNES was associated with aortic vasodilation and renal vasoconstriction. This response differs in SHRs, where we did not observe ABF and AVC changes (CONTROL or POST-KYN). Thus, we demonstrate that in the EPR, ABF, RBF, AVC, and RVC responses of normotensive and spontaneously hypertensive rats are distinct, and contralateral RVLM to the active musculature of these animals, participates in the responses of aortic vasodilation and renal vasoconstriction in normotensive rats, but does not significantly influence BF variations in SHR. In addition, the 15-day treatment with the nitric oxide (NO) donor and NBL selective beta blocker was also not able to alter the hemodynamic responses in SHRs.Item O envolvimento do núcleo paraventricular do hipotálamo na manutenção da pressão arterial e modulação do tônus simpático renal de ratos tratados com dieta rica em sódio na fase pós natal(Universidade Federal de Goiás, 2019-06-28) Almeida, Melissa Tavares; Mourão, Aline Andrade; http://lattes.cnpq.br/1596884578398481; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Ferreira-Neto, Marcos Luiz; Mendes, Elizabeth Pereira; Pedrino, Gustavo RodriguesHigh sodium intake can affect the excitability of neurons in regions responsible for the control of sympathetic nervous activity. It is known that the neuronal activity of the hypothalamus paraventricular nucleus (PVN) is increased in several models of sodium-sensitive arterial hypertension (SSH). Diseases that develop in adulthood are related to certain exposures suffered by the individual during the early stages of life. However, the literature point out differences between males and females in the expression of hypertension in both animal and human models, and in females, estrogen sometimes has a cardioprotective effect. In the present study, we investigated whether changes in diet during the postnatal phases contribute to central alterations in the control of renal sympathetic tone in males and females, and whether they persist in adulthood. More specifically, we evaluated the contribution of the PVN in the control of cardiovascular parameters and sympathetic nervous activity (SNA) after treatment with a sodium-rich diet for 30 days in adult rats and rats. Twenty one days old wistar male and female rats were divided into two groups: control group, composed of males (MCTRL) and females (FCTRL), maintained with water; and experimental group, composed of males (MEXP) and females (FEXP), maintained with hypertonic solution of 0.3 M NaCl. Animals of all groups received chow and hypertonic solution or water ad libitum for 30 days. After treatment, the animals of all groups were maintained with water and chow for 15 days (recovery period). Daily food and fluid (0.3 M NaCl or water) intake and body weight were monitored during the treatment and recovery periods. At the end of treatment, the treated male rats were found to have lower body weight compared to controls (MEXP (n = 9): 115.3 ± 4.7 g vs. MCTRL (n = 9): 168.0 ± 8.0 g, p <0.05). However, this difference was not observed between the experimental and control female groups (FEXP (n = 8): 119.5 ± 5.3 g vs. FCTRL (n = 8): 134.1 ± 5.2 g). We also observed that the experimental animals ingested a greater amount of fluid per gram of body weight (bw) than control animals MEXP (n=9): 0.717 ± 0.120 mL/g/bw vs. MCTRL (n=9): 0.209; FEXP (n=8): 0.576 ± 0.060 mL/g/bw vs. FCTRL (n=8): 0.251 ± 0.011 mL/g/bw, p < 0.05) and we observed a decrease in the excreted volume (Vexc) in experimental females compared to the ingested volume (Ving) (FEXP (n=8): Ving 89.6 ± 5.6 mL vs. Vexc 56.8 ± 5.2 mL, p < 0.05). In the recovery period there was no difference in daily water intake between groups (MEXP (n=9): 0.203 ± 0.008 mL/g/bw vs. MCTRL (n=9): 0,171 ± 0.005 mL/g/bw; FEXP (n=8): 0,229 ± 0,013 mL/g/bw vs. FCTRL (n=8): 0.187 ± 0,010 mL/g/bw). In another set of experiments, we evaluated the participation of the PVN in the maintenance of sympathetic tonus after treatment with a high sodium diet for 30 days. Bilateral nanoinjections of 50 nL of muscimol (GABAA agonist, 4 mM) were performed in the PVN in experimental and control animals during recording of mean arterial pressure (MAP), heart rate (HR) and renal SNA (RSNA). It is noteworthy that in the females these experiments were performed in the diestrus of the estrous cycle. In the anaesthetized experiments, the males of the treated group showed higher values of baseline MAP compared to both control male group and to female groups (PAM: MEXP (n=6): 108.2 ± 2.9 mmHg vs. MCTRL (n=6): 92 ± 5.4 mmHg vs. FEXP (n=6): 102.7 ± 4.4 mmHg vs. FCTRL (n=6): 90.8 ± 1.8 mmHg, p<0.05). Inhibition of the PVN promoted a reduction on MAP of experimental groups when compared to control groups: (Δ MAP: MEXP (n=6): -14.9 ± 1.5 mmHg vs. MCTRL (n=6): -7.2 ± 0.7 mmHg vs. FEXP (n=6): -12.9 ± 1.7 mmHg vs. FCTRL (n=6): -4.8 ± 0.6 mmHg, p <0.05). On the other hand, no differences were observed in the HR responses of the evaluated groups (Δ HR: MEXP (n=6): -35.8 ± 6.6 bpm vs. MCTRL (n=6): -21.6 ± 2.9 bpm vs. FEXP (n=6): -27.8 ± 3.5 bpm vs. FCTRL (n=6): -31.0 ± 4.4 bpm). In addition, acute inhibition of PVN promoted renal sympathoinhibition in experimental animals compared to controls (Δ % ANSR: MEXP (n=6): -17.3 ± 1.5% vs. MCTRL (n=6): -6.8 ± 1.0% vs. FEXP (n=6): -18.1 ± 0.5% vs. FCTRL (n=6): -3.0 ± 0.6%, p <0.05). The results demonstrated in the present study showed that the hypersodiuc diet during the early stages of life altered baseline MAP of experimental males. Additionally, we observed that the acute inhibition of PVN promoted cardiovascular and sympathetic changes in rats treated with a high sodium diet in comparison to the control group. Taken together, the observed results add new information to the literature and suggest that cardiovascular and sympathetic control regions, such as the PVN, may be more involved in the tonic modulation of blood pressure and RSNA in response to sodium overload in the postnatal phase of normotensive rats. Finally, our study points to the possibility that estrogen may have helped decrease the high blood pressure promoted by prolonged increase in sodium intake, but it was not enough to prevent the increase in the modulation of the sympathetic tone exerted by the PVN. However, future studies are needed to investigate pathways and mechanisms involved in these responses.Item Avaliação das respostas cardiovasculares e eletroencefalográficas após crises epilépticas induzidas pelo abrasamento elétrico da amígdala em diferentes fases do ciclo sono-vigília de ratos(Universidade Federal de Goiás, 2016-09-21) Ghazale, Poliana Peres; Pansani, Aline Priscila; http://lattes.cnpq.br/6385679829734771; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Colugnati, Diego Basile; Blanch, Graziela Torres; Oliveira, André Henrique Freiria; Pansani, Aline PriscilaIntroduction: Cardiovascular alterations have been identified as the main cause of Sudden Unexpected Death in Epilepsy (SUDEP). There is an intimate relationship between epilepsy and sleep. Most cases of SUDEP occurs during sleep and the NREM sleep is a facilitator factor for the occurence of seizures. Aim: To evaluate cardiovascular and electroencephalographic responses of rats submitted to kindling model induced at diferente stages of sleep-wake cycle. Methods: The experimental protocol was approved by Ethics Commitee of the Universidade Federal de Goiás (CEUA-035/2015). Wistar rats (250-350 g) were separeted into 4 groups and seizures were induced according to sleep-wake cycle (Wake, NREM sleep and REM sleep) or no seizure (SHAM). We used the kindling model for induction of seizures. The animals was submitted to stereotactic surgery to implant electrodes in the right amygdala, for electrical stimulation, and in the cortex, for electroencephalographic record (EEGc). Electrodes for electromyographic (EMG) and electrocardiographic (ECG) recordings were also implanted. The detection of sleep phase was based on algorithms described by Louis et al. (2003). The electrical stimulus was induced one time per day and consisted in a biphasic wave during 2 seconds (60 Hz). The seizures evolution was analyzed according to Racine’s scale (E1: orofacial movements; E2: mastigatory movements and head clonus; E3: forelimb clonus; E4: rearing; E5: rearing and falling). Three E5 seizures was induced in each animal. We evaluated heart rate (HR), heart rate variability (HRV) arrhythmias and EEGc in vivo, cardiac function and vascular reactivity ex vivo. Results: The time fully kindling in NREM group was lower compared to Wake group. The NREM group presents postictal tachycardia in the early stages of process. The duration of postictal generalized electroencephalogram supression (PGES) is larger in REM group. The PGES in Wake group was accompanied by a decrease in HR compared to the final period of seizures. The muscle cell in aortic artery of Wake group had greater contraction capacity than the other groups, while the REM group had a higher endothelium-dependent relaxatio. Parameters such as after-discharge duration (AD), HR and HRV after kindling process, arrhythmias, bradycardia followed by tachycardia during the ictal period of E5 seizures and ex vivo cardiac funtion were similar in all groups. Conclusion: Our results suggest that kindling process per se was able to induce an increase in post-ictal HR in NREM group, an increase in PGES duration in REM group, and an impairment on vascular reactivity of NREM (higher contraction percentage) and REM (lower relaxation percentage) groups.Item Avaliação de alterações cardiovasculares relacionadas ao efeito de drogas antiepilépticas em ratos submetidos ao modelo de indução de epilepsia pela pilocarpina(Universidade Federal de Goiás, 2018-05-18) Souza, Beatriz Pacheco de; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Lino Júnior, Ruy de Souza; Castro, Carlos Henrique de; Colugnati, Diego BasileEpilepsy is one of the most common problems in the neurological clinic, affecting up to 1% of the world population, moreover, individuals with epilepsy have a higher mortality than the general population. Thus, the interest in investigating cardiac changes in patients with epilepsy has been increasing, and some studies have associated the use of antiepileptic drugs (AEDs) with cardiovascular disorders. In this context, there are hypotheses that patients using specific AEDs, sodium channel blockers, have an increased risk of cardiovascular disease (CVD). In our study, we sought to evaluate cardiovascular responses in epileptic rats submitted to chronic administration of carbamazepine (CBZ) or lamotrigine (LTG). Baseline cardiovascular parameters [Systolic blood pressure (SBP); Diastolic blood pressure (DBP); Mean arterial pressure (MAP) and heart rate (HR)] were recorded through cannulation of the femoral artery and electrode implant after sixty days of treatment with AED or vehicle [(150mg / kg (vo)]. The animals were submitted to a baroreflex test with bolus administration of phenylephrine (PHE - 5μg) and sodium nitroprusside (NPS - 10μg) via cannulation of the femoral vein and later submitted to a challenge with isoproterenol. Through the recording of baseline cardiovascular parameters, we also analyzed the heart rate variability (HRV) and the number of extrasystoles. After all procedures in vivo, samples of the heart were retained for histological analyzes of cardiac tissue. The division of the groups was performed in controls without epilepsy (CNT), epileptics (EP), epileptics treated with CBZ (CBZ) and epileptics treated with LTG (LTG). In our results the epileptic rats presented all the baseline cardiovascular parameters higher than the parameters of animals without epilepsy. CBZ treatment reduced resting HR, SBP and MAP compared to untreated epileptic animals. Treatment with LTG also reduced resting HR compared to the EP group. We also observed that the EP group had a greater cross-sectional area (CSA) of cardiomyocytes when compared to the other groups and an increased accumulation of perivascular collagen in comparison to CNT and CBZ groups. In this way, we can suggest that chronic use of AEDs may influence cardiovascular responses and cardiac microstructure.Item Avaliação da reatividade coronariana do coração isolado de ratos submetidos ao modelo de indução de epilepsia pela pilocarpina(Universidade Federal de Goiás, 2016-09-19) Vitorino, Paula Rodrigues; Pedrino, Gustavo Rodrigues; http://lattes.cnpq.br/1155446449250341; Colugnati, Diego Basile; http://lattes.cnpq.br/3875833705952056; Magalhães, Fernando Henrique; Pansani, Aline Priscila; Colugnati, Diego BasileEpilepsy is the most common chronic neurological disease in the world, characterized by paroxysmal, excessive and synchronous discharges of a neuronal population that leads to spontaneous and recurrent seizures. Sudden unexpected death in epilepsy (SUDEP) is responsible for 7.5% to 17% of deaths in epilepsy. Although the pathophysiological mechanisms are unknown, one possible explanation is that they are of cardiogenic origin. Some studies relate cardiac abnormalities with seizures, and these may be responsible for Suped, and as yet has no works that have investigated the control of coronary flow of patients or in experimental models of epilepsy, and as coronary heart disease listed as one of the main causes of sudden death in the world population, assess coronary flow in experimental epilepsy model becomes important for the understanding of SUDEP. So this study aims to evaluate the coronary reactivity, ventricular function and cardiac tissue of rats submitted to the pilocarpine model of epilepsy. The animals were separated into two groups: control (n = 8) and epilepsy (n = 8). It was administered 350 mg/kg of pilocarpine (i.p) preceded by 1mg/kg methylscopolamine (s.c) in both groups, animals that entered in status epilepticus received diazepam 10 mg/kg (i.p) after 3 hours to block it. After that, the animals were placed in a room for video monitoring (24 h/day) until complete two months of epilepsy (epilepsy group). Rats that received pilocarpine and did not develop status epilepticus comprised the control group, being housed in the same animal environment that epilepsy group. At two months of chronic epilepsy rats were sacrificed and the heart dissected to the Langendorff preparation (constant flow), after a 35 minutes of stabilization in a Krebs - Ringer solution bradykinin (BK) was administered (10ˉ⁸, 10ˉ⁷, 10ˉ⁶ and 10ˉ⁵M) in bolus and after of washout was treated with sodium nitroprusside in different concentrations (10ˉ⁶, 10ˉ⁵, 10ˉ⁴ and 10ˉ³M) also bolus. They were found in animals with epilepsy a significant reduction in coronary relaxation by BK infusion at a concentration 10ˉ⁵M. It was observed that rats with epilepsy have increased perivascular collagen, larger cardiomyocytes, and more coronary arteries, with no change of nitric oxide synthase endoletial (eNOS), superoxide dismutase (SOD) and catalase expression. Thus, our results show reduction of coronary relaxation induced by bradykinin which leads us to believe in loss of endothelial function of these animals, since, we did not observe differences in relaxation induced by sodium nitroprusside, despite the perivascular fibrosis of epileptic rats.Item Avaliação dos efeitos de peptídeos isolados de veneno de serpentes no sistema cardiovascular de ratos(Universidade Federal de Goiás, 2016-03-22) Alves, Pedro Henrique; Ianzer, Danielle Alves; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4760882T6; Alves, Carlos Henrique; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4758015Z0; Castro, Carlos Henrique de; Ianzer, Danielle Alves; Ghedini, Paulo CesarThe proline-riche-oligopeptides (PROs) were identified in the crude venom of snakes Bothrops jararaca (Bj), Bothrops cotiara (Bc) and Bothrops fonsecai (Bf). Previous studies have shown hypotensive/antihypertensive effects of the PROs in normotensive and hypertensive (SHR) rats. However, the direct effect of PROs in the aorta and heart isolated, as well as, the action mechanisms involved in these effects is unknown. In the presenty study, were evaluated the cardiovascular effect of six PROs, Bj-PRO-5a,-7a,-10c, Bc-PRO-10e, Bf-PRO-10d,-10f. The aortic rings, with (E+) or without (E-) endothelium, were preconstricted with phenylephine (Phe, 0.1 μmol/L), following increasing concentrations of PROs (0.1 nmol/L – 1 μmol/L) in presence or absence of a nonselective antagonist muscarinic receptors (Atropine, 3µmol/L), M1 muscarinic receptor antagonist (Pirenzepine, 1 µmol/L), synthase nitric oxide inhibitor (L-NAME, 1 µmol/L), adenylyl cyclase inhibitor (MDL 12.330A, 3 µmol/L), guanylyl cyclase inhibitor (ODQ, 3µmol/L) or argininosuccinate synthetase inhibitor (MDLA, 1 µmol/L). To evaluated the coronary and cardiac contractility effects of PROs, the hearts were perfused according Langendorff technique. The hearts were perfused for a basal period with Krebs Ringer solution containing the PROs (0.05 or 5 nmol/L) in presence or absence of L-NAME (10 nmol/L), ODQ (200 nmol/L) or MDL (1 µmol/L). The PROs utilized in this study induced endothelium-dependend vasorelaxation in aortic rings of Wistars and SHRs. Atropine and pirezenpine blocked the vasorelaxant effect of Bj-PRO-7a in isolated aorta from Wistar and SHR. L-NAME, ODQ or MDL inhibited the aortic vasorelaxation induced by Bj-PRO-7a and Bj-PRO-10c in both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings of SHR, but not in Wistar. Just the peptides Bj-PRO-7a and Bj-PRO-10c promoted a significant coronary vasodilatation in isolated heart from Wistar and SHR rats. The coronary vasodilatation induced by Bj-PRO-7a was inhibited in the presence of L-NAME in isolated heart from Wistar. Already in isolated heart from SHR this effect was abolished by L-NAME, ODQ or MDL. The Bc-PRO-10e and Bf-PRO-10f did not induce significant effects on cardiac contractility. However, the Bj-PRO-5a, -7a, -10c and Bf-PRO-10f promoted negative inotropic effect in the isolated hearts from Wistar and/or SHR. This effect in isolated hearts perfused by Bj-PRO-7a was inhibited in the presence of L-NAME in Wistars. Differently, the effect of Bj-PRO-10c was blocked by L-NAME, ODQ or MDL in both strains. Sumarizing, the PROs utilized in this study induced endothelium-dependend vasorelaxation. The data demonstrated participation of pathways NO/GCs/GMPc and AC/AMPc in the vasorelaxant effect of peptides Bj-PRO-7a and Bj-PRO-10c. In addition, the muscarinic receptors are involved in the vasorelaxant effects induced by peptide Bj-PRO-7a in aortic rings from Wistar and SHR rats. Moreover, the negative inotropic effect induced by Bj-PRO-7a and Bj-PRO-10c is linked with activation of NO in cardiomyocyte of normotensive and hypertensive rats.