Browsing by Author "Colombari, Eduardo"
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Item Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii.(1997) Machado, Benedito Honório; Chianca Júnior, Deoclécio Alves; Haibara, Andréa Siqueira; Mauad, Helde; Colombari, EduardoThe nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation. The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular reflex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamate microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory component of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.Item Baroreflex function in conscious rats submitted to iron overload.(2005) Cardoso, Leonardo Máximo; Pedrosa, Maria Lúcia; Silva, Marcelo Eustáquio; Moraes, Márcio Flávio Dutra; Colombari, Eduardo; Chianca Júnior, Deoclécio AlvesOur hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 µg/kg) or sodium nitroprusside (1.0 to 10.0 µg/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 ± 0.74 and -7.93 ± 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 ± 0.3 sham vs -3.6 ± 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity.Item Cardiopulmonary reflex is attenuated in iron overload conscious rats.(2013) Cardoso, Leonardo Máximo; Fernandes, Luciano Gonçalves; Alves, Arthur Moreira; Pedrosa, Maria Lúcia; Silva, Marcelo Eustáquio; Colombari, Eduardo; Moraes, Márcio Flávio Dutra; Chianca Júnior, Deoclécio AlvesIncreased iron intake can lead to iron accumulation in serum and tissues. Its has been described that serum and tissue iron overload increase reactive oxygen species (ROS) levels and reduce the effectiveness of the cardiovascular neural mechanisms involved in the maintenance of the arterial blood pressure whithin a narrow range of variation, therefore, iron overload may disrupt cardiovascular homeostasis contributing to physiopathological status development. In the present study we evaluated whether iron accumulated in serum or tissue of awake animals affect the cardiovascular homeostasis through changes in the cardiopulmonary reflex (CPR). We observed that the CPR is reduced in both serum and tissue iron overloaded groups, but no changes were found in the left ventricular pressure measurements, suggesting that iron-related effects are restrict to the CPR neural pathways.We also observed that the serum overloaded group presented lower basal heart rate levels, suggesting an increased parasympathetic efferent activity directed to the heart in this group. Taken together, our data suggest an important role for the iron-generated ROS to the cardiovascular homeostasis, especially regarding the CPR in awake animals.Item Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats.(2006) Cardoso, Leonardo Máximo; Colombari, Débora Simões de Almeida; Menani, José Vanderlei; Chianca Júnior, Deoclécio Alves; Colombari, EduardoReactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H2O2) injected alone or combined with the anti-oxidant agent N-acetil-l-cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H2O2 into the 4th V was also investigated. Male Holtzman rats (280–320 g) with a stainless steel cannula implanted into the 4th V and polyethylene cannulas inserted into the femoral artery and vein were used. Injections of H2O2 (0.5, 1.0 and 1.5 _mol/0.2 _L, n = 6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 _mol doses of H2O2 also produced a long lasting bradycardia (at least 24 h with the high dose of H2O2). Prior injection of N-acetyl-l-cysteine (250 nmol/1 _L/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H2O2 (1_mol/0.5 _L/rat, n = 7) into the 4th V. Intravenous (i.v.) atropine methyl bromide (1.0 mg/kg, n = 11) abolished the bradycardia but did not affect the pressor response to H2O2. Prazosin hydrochloride (1.0 mg/kg, n=6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 _L/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H2O2. The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses.Item Cardiovascular responses to hydrogen peroxide into the nucleus tractus solitarius.(2009) Cardoso, Leonardo Máximo; Colombari, Débora Simões de Almeida; Menani, José Vanderlei; Toney, Glenn M.; Chianca Júnior, Deoclécio Alves; Colombari, EduardoThe nucleus tractus solitarius (NTS), a major hindbrain area involved in cardiovascular regulation, receives primary afferent fibers from peripheral baroreceptors and chemoreceptors. Hydrogen peroxide (H(2)O(2)) is a relatively stable and diffusible reactive oxygen species (ROS), which acting centrally, may affect neural mechanisms. In the present study, we investigated effects of H(2)O(2) alone or combined with the glutamatergic antagonist kynurenate into the NTS on mean arterial pressure (MAP) and heart rate (HR). Conscious or anesthetized (urethane and alpha-chloralose) male Holtzman rats (280-320 g) were used. Injections of H(2)O(2) (125 to 1500 pmol/40 nl) into the intermediate NTS of anesthetized rats evoked dose-dependent and transient hypotension (-18 +/- 3 to -55 +/- 11 mmHg) and bradycardia (-16 +/- 5 to -116 +/- 40 bpm). Injection of the catalase inhibitor 3-amino-1,2,4-triazole (100 nmol/40 nl) into the NTS also produced hypotension and bradycardia. Previous injection of the ionotropic L-glutamate receptor antagonist kynurenate (7 nmol/40 nl) attenuated by 48% the bradycardic response, without changing the hypotension evoked by H(2)O(2) (500 pmol/40 nl) in anesthetized rats. The antioxidant L-ascorbate (600 pmol/80 nl) injected into the NTS attenuated the bradycardic (42%) and hypotensive (67%) responses to H(2)O(2) (500 pmol/40 nl) into the NTS. In conscious rats, injection of H(2)O(2) (50 nmol/100 nl) into the NTS also evoked intense bradycardia (-207 +/- 8 bpm) and hypotension (-54 +/- 6 mmHg) that were abolished by prior injection of kynurenate (7 nmol/100 nl). The results show that H(2)O(2) into the NTS induces hypotension and bradycardia probably due to activation of glutamatergic mechanisms.Item Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats.(2011) Giusti, Marcelo Franchini; Sato, Monica Akemi; Cardoso, Leonardo Máximo; Braga, Valdir de Andrade; Colombari, EduardoBaroreceptor reflex is an important system for neural control of blood pressure. Recently, reactive oxygen species (ROS) have been shown to play an important role in neuronal activity of central areas related to blood pressure control. The aim of this study was to investigate the effects elicited by ascorbic acid (AAC) and N-acetylcysteine (NAC) injections into the 4thV on the parasympathetic component of the baroreflex. Male Wistar rats were implanted with a stainless steel guide cannula into the 4thV. One day prior to the experiments, the femoral artery and vein were cannulated for pulsatile arterial pressure, mean arterial pressure and heart rate measurements and drug administration, respectively. After baseline recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 3_g/kg, i.v.) and a depressor dose of sodium nitroprusside (SNP, 30_g/kg, i.v.) before (control) and 5, 15, 30 and 60 min after AACorNACinto the 4thV. ControlPHEinjection induced baroreflex-mediated bradycardia (−93±13 bpm, n = 7). Interestingly, after AAC injection into the 4thV, PHE injection produced a transient tachycardia at 5 (40±23 bpm), 15 (26±22 bpm) and 30 min (59±21 bpm). No changes were observed in baroreflexmediated tachycardia evoked by SNP after AAC injection on 4thV (control: 151±23bpm vs. 135±18bpm at 5 min after AAC, n = 7). In the NAC treated group, PHE induced a reduction in reflex bradycardia at 5 min when compared to control (−11±17bpm vs. −83±15 bpm, n = 7). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after NAC injection on 4thV. The antioxidants AAC and NAC may act in the central nervous system affecting the parasympathetic component of the cardiac baroreflex.Item Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate.(2012) Cardoso, Leonardo Máximo; Colombari, Eduardo; Toney, Glenn M.Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates sympathetic nerve activity responses to L-glutamate. J Appl Physiol 113: 1423–1431, 2012. First published September 13, 2012; doi:10.1152/japplphysiol.00912.2012.—The hypothalamic paraventricular nucleus (PVN) is important for maintenance of sympathetic nerve activity (SNA) and cardiovascular function. PVNmediated increases of SNA often involve the excitatory amino acid L-glutamate (L-glu), whose actions can be positively and negatively modulated by a variety of factors, including reactive oxygen species. Here, we determined modulatory effects of the highly diffusible reactive oxygen species hydrogen peroxide (H2O2) on responses to PVN L-glu. Renal SNA (RSNA), arterial blood pressure, and heart rate were recorded in anesthetized rats. L-Glu (0.2 nmol in 100 nl) microinjected unilaterally into PVN increased RSNA (P 0.05), without affecting mean arterial blood pressure or heart rate. Effects of endogenously generated H2O2 were determined by comparing responses to PVN L-glu before and after PVN injection of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ; 100 nmol/200 nl, n 5). ATZ alone was without effect on recorded variables, but attenuated the increase of RSNA elicited by PVN L-glu (P 0.05). PVN injection of exogenous H2O2 (5 nmol in 100 nl, n 4) and vehicle (artificial cerebrospinal fluid) were without affect, but H2O2, like ATZ, attenuated the increase of RSNA to PVN L-glu (P 0.05). Tonic effects of endogenous H2O2 were determined by PVN injection of polyethylene glycol-catalase (1.0 IU in 200 nl, n 5). Whereas polyethylene glycol-catalase alone was without effect, increases of RSNA to subsequent PVN injection of L-glu were increased (P 0.05). From these data, we conclude that PVN H2O2 tonically, but submaximally, suppresses RSNA responses to L-glu, supporting the idea that a change of H2O2 availability within PVN could influence SNA regulation under physiological and/or disease conditions.Item Espécies reativas de oxigênio no controle neurovegetativo da pressão arterial.(2006) Cardoso, Leonardo Máximo; Colombari, Débora Simões de Almeida; Menani, José Vanderlei; Paula, Patricia Maria de; Chianca Júnior, Deoclécio Alves; Colombari, EduardoExistem evidências de que a atividade neuronal pode ser modulada pelo estado redox (balanço entre espécies químicas oxidantes e redutoras) das células, influenciando, assim, as diferentes funções biológicas que são controladas pelo sistema nervoso. Essa modula- ção pode ocorrer por meio de diferentes mecanismos e um deles é a modulação da transmiss ão sináptica no sistema nervoso central (SNC). As descargas autonômicas que são controladas por mecanismos localizados em diferentes áreas do SNC são fundamentais para o controle da pressão arterial. Um importante neurotransmissor que participa dos mecanismos centrais de controle cardiovascular é o glutamato e a transmissão glutamatérgica pode ser extensamente afetada por espécies reativas de oxigênio, oxidantes que parecem ter um importante papel em processos fisiológicos e patológicos. No presente artigo são apresentados os principais achados experimentais que suportam a hipótese de que as espécies reativas de oxigênio podem modular as funções cardiovasculares por produzir alterações nos mecanismos centrais de controle dos sistemas simpático e parassimpático. Logo, desequilíbrios na sinalização mediada por espécies reativas de oxigênios podem contribuir para o desenvolvimento de doenças cardiovasculares como a hipertensão.Item Inhibition of central angiotensin II-induced pressor responses by hydrogen peroxide.(2010) Lauar, M. R.; Colombari, Débora Simões de Almeida; Paula, Patricia Maria de; Colombari, Eduardo; Cardoso, Leonardo Máximo; Luca Junior, L. A. de; Menani, José VanderleiHydrogen peroxide (H2O2), important reactive oxygen species produced endogenously, may have different physiological actions. The superoxide anion (O2 •_) is suggested to be part of the signaling mechanisms activated by angiotensin II (ANG II) and central virus-mediated overexpression of the enzyme superoxide dismutase (that dismutates O2 •_ to H2O2) reduces pressor and dipsogenic responses to central ANG II. Whether this result might reflect elevation of H2O2 rather than depletion of O2 •_ has not been addressed. Here we investigated the effects of H2O2 injected intracerebroventricularly (i.c.v.) or ATZ (3-amino-1,2,4-triazole, a catalase inhibitor) injected intravenously (i.v.) or i.c.v. on the pressor responses induced by i.c.v. injections of ANG II. Normotensive male Holtzman rats (280–320 g, n_5–13/ group) with stainless steel cannulas implanted in the lateral ventricle were used. Prior injection of H2O2 (5 _mol/1 _l) or ATZ (5 nmol/1 _l) i.c.v. almost abolished the pressor responses induced by ANG II (50 ng/1 _l) also injected i.c.v. (7_3 and 5_3 mm Hg, respectively, vs. control: 19_4 mm Hg). Injection of ATZ (3.6 mmol/kg b.wt.) i.v. also reduced central ANG II-induced pressor responses. Injections of H2O2 i.c.v. and ATZ i.c.v. or i.v. alone produced no effect on baseline arterial pressure. Central ANG II, H2O2 or ATZ did not affect heart rate. The results show that central injections of H2O2 and central or peripheral injections of ATZ reduced the pressor responses induced by i.c.v. ANG II, suggesting that exogenous or endogenous H2O2 may inhibit central pressor mechanisms activated by ANG II.Item Iron overload in hypercholesterolemic rats affects iron homeostasis and serum lipids but not blood pressure.(2003) Ribeiro, Silvana Mara Luz Turbino; Silva, Marcelo Eustáquio; Chianca Júnior, Deoclécio Alves; Paula, Heberth de; Cardoso, Leonardo Máximo; Colombari, Eduardo; Pedrosa, Maria LúciaEpidemiologic and experimental data suggest that excess iron may contribute to the development of cardiovascular diseases (CVD). Because increased LDL cholesterol, decreased HDL cholesterol and alteration of systolic blood pressure (SBP) have all been implicated as risk factors for atherosclerosis and related CVD, the present study was designed to determine whether excess iron alters serum lipids and SBP in control and hypercholesterolemic rats. Female Fischer rats were divided into four groups. The control group (C) was fed the control diet, the CI group was fed the control diet and given iron dextran injections, the hypercholesterolemic group (H) was fed a 1 g/100 g cholesterol diet, and the HI group was fed the cholesterol diet and given iron dextran injections. The rats were fed the diets for 8 wk and iron dextran injections were given during wk 6 at doses of 10 mg/d for 5 d. Excess iron reduced (P 0.01) plasma total cholesterol in rats fed the cholesterol diet (5.31 0.83 and 3.17 0.31 mmol/L for H and HI, respectively). Excess iron also resulted in a redistribution of cholesterol among the various lipoprotein fractions, with an increase (P 0.01) in HDL cholesterol (0.56 0.12 and 0.85 0.16 mmol/L for H and HI, respectively) and a decrease (P 0.01) in LDL cholesterol (4.49 0.77 and 2.09 0.26 mmol/L for H and HI, respectively). This redistribution also occurred in the rats fed the control diet. The treatments did not affect SBP or heart rate. The high cholesterol diet affected iron homeostasis; group H had lower transferrin saturation than group C (P 0.01); group HI had a lower serum iron concentration than group CI but did not differ from group H (P 0.05). Therefore, we conclude that if iron has any effect on CVD, it is not through its influence on serum lipids and blood pressure.Item A low protein diet causes an increase in the basal levels and variabiltiy of mean arterial pressure and heart rate in fisher rats.(2013) Oliveira, Eduardo Luiz de; Cardoso, Leonardo Máximo; Pedrosa, Maria Lúcia; Silva, Marcelo Eustáquio; Dun, Nae J.; Colombari, Eduardo; Moraes, Márcio Flávio Dutra; Chianca Júnior, Deoclécio AlvesThe correlation between nutrition and cardiovascular related disorders is a well-established fact. Previous work from our Laboratory has suggested a significant compromise of cardiovascular reflexes in conscious rats submitted to a low-protein (LP) diet. Our working hypothesis is that the basal level of mean arterial pressure (MAP), variability of the mean arterial pressure (VMAP), heart rate (HR) and variability of heart rate (VHR) are altered in rats submitted to a protein restricted diet. Two experimental groups were used: control group (normal protein 15%, NP) and malnourished group (lowprotein 6%, LP). In order to verify the efficiency of the dietary restriction we measured body weight, total blood protein, plasma albumin, urea and glucose. Our experiments demonstrated that the malnourished rats presented augment levels of basal MAP (LP 122 6 2mmHg vs. NP 113 6 1mmHgÞ and of VMAP (LP 12:8 6 1:5mmHg vs. NP 9 6 1mmHgÞ when compared to the control group. We observed similar increased levels, in the malnourished group, for both HR (LP 429 6 8bpm vs. NP 381 6 7bpmÞ and VHR (LP 67:6 6 8:3bpm vs. NP 44:4 6 4:9bpmÞ: Our results suggest a correlation between the LP diet in Fisher rats and the increased basal levels of mean arterial pressure, HR and their respective variability.Item NMDA receptors in NTS are involved in the bradycardic but not in the pressor response of chemoreflex.(1995) Haibara, Andréa Siqueira; Colombari, Eduardo; Chianca Júnior, Deoclécio Alves; Bonagamba, Leni Gomes Heck; Machado, Benedito HonórioActivation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid @P-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dosedependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component of the chemoreflex in the commissural NTS is mediated by NMDA receptors, whereas pressor and ventilatory responses are not.