Chagas disease (CD) is caused by the parasitic protozoan T. cruzi. The progression of CD in ~30% of patients results in Chagasic Cardiomyopathy (CCM). Currently, it is known that the inflammatory system plays a significant role in the... more
Chagas disease (CD) is caused by the parasitic protozoan T. cruzi. The progression of CD in ~30% of patients results in Chagasic Cardiomyopathy (CCM). Currently, it is known that the inflammatory system plays a significant role in the CCM. Interferon-gamma (IFN-γ) is the major cytokine involved in parasitemia control but has also been linked to CCM. The L-type calcium current (ICa,L) is crucial in the excitation/contraction coupling in cardiomyocytes. Thus, we compared ICa,L and the mechanical properties of cardiomyocytes isolated from infected wild type (WT) and IFN-γ(−/−) mice in the first stage of T. cruzi infection. Using the patch clamp technique, we demonstrated that the infection attenuated ICa,L in isolated cardiomyocytes from the right and left ventricles of WT mice at 15 days post-infection (dpi), which was not observed in the IFN-γ(−/−) cardiomyocytes. However, ICa,L was attenuated between 26 and 30 dpi in both experimental groups. Interestingly, the same profile was obse...
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Clinical and preclinical studies have shown that patients with Diabetic Neuropathy Pain (DNP) present with increased tumor necrosis factor alpha (TNF-α) serum concentration, whereas studies with diabetic animals have shown that TNF-α... more
Clinical and preclinical studies have shown that patients with Diabetic Neuropathy Pain (DNP) present with increased tumor necrosis factor alpha (TNF-α) serum concentration, whereas studies with diabetic animals have shown that TNF-α induces an increase in NaV1.7 sodium channel expression. This is expected to result in sensitization of nociceptor neuron terminals, and therefore the development of DNP. For further study of this mechanism, dissociated dorsal root ganglion (DRG) neurons were exposed to TNF-α for 6 h, at a concentration equivalent to that measured in STZ-induced diabetic rats that developed hyperalgesia. Tetrodotoxin sensitive (TTXs), resistant (TTXr) and total sodium current was studied in these DRG neurons. Total sodium current was also studied in DRG neurons expressing the collapsin response mediator protein 2 (CRMP2) SUMO-incompetent mutant protein (CRMP2-K374A), which causes a significant reduction in NaV1.7 membrane cell expression levels. Our results show that TN...
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Background and PurposeThe artemisinin derivative, artemether, has antimalarial activity with potential neurotoxic and cardiotoxic effects. Artemether in nanocapsules (NC‐ATM) is more efficient than free artemether for reducing... more
Background and PurposeThe artemisinin derivative, artemether, has antimalarial activity with potential neurotoxic and cardiotoxic effects. Artemether in nanocapsules (NC‐ATM) is more efficient than free artemether for reducing parasitaemia and increasing survival of Plasmodium berghei‐infected mice. NCs also prevent prolongation of the QT interval of the ECG. Here, we assessed cellular cardiotoxicity of artemether and how this toxicity was prevented by nanoencapsulation.Experimental ApproachMice were treated with NC‐ATM orally (120 mg·kg−1 twice daily) for 4 days. Other mice received free artemether, blank NCs, and vehicle for comparison. We measured single‐cell contraction, intracellular Ca2+ transient using fluorescent Indo‐1AM Ca2+ dye, and electrical activity using the patch‐clamp technique in freshly isolated left ventricular myocytes. The acute effect of free artemether was also tested on cardiomyocytes of untreated animals.Key ResultsArtemether prolonged action potentials (AP...
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Background. Cardiomyopathies remain among the leading causes of death worldwide, despite all efforts and important advances in the development of cardiovascular therapeutics, demonstrating the need for new solutions. Herein, we describe... more
Background. Cardiomyopathies remain among the leading causes of death worldwide, despite all efforts and important advances in the development of cardiovascular therapeutics, demonstrating the need for new solutions. Herein, we describe the effects of the redox-active therapeutic Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, AEOL10113, BMX-010 (MnTE-2-PyP5+), on rat heart as an entry to new strategies to circumvent cardiomyopathies. Methods. Wistar rats weighing 250-300 g were used in both in vitro and in vivo experiments, to analyze intracellular Ca2+ dynamics, L-type Ca2+ currents, Ca2+ spark frequency, intracellular reactive oxygen species (ROS) levels, and cardiomyocyte and cardiac contractility, in control and MnTE-2-PyP5+-treated cells, hearts, or animals. Cells and hearts were treated with 20 μM MnTE-2-PyP5+ and animals with 1 mg/kg, i.p. daily. Additionally, we performed electrocardiographic and echocardiographic analysis. Results. Using isolated rat cardiomyocytes...
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ABSTRACT: Rats and mice are the most common species used in experimental cardiac electrophysiology studies. Electrocardiogram (ECG) recording shows paramount importance for monitoring arrhythmias and cardiac function in several disease... more
ABSTRACT: Rats and mice are the most common species used in experimental cardiac electrophysiology studies. Electrocardiogram (ECG) recording shows paramount importance for monitoring arrhythmias and cardiac function in several disease models, including QT syndrome. However, the lack of standardized reference values and QT correction formula for different animal species and lineages represent a challenge for ECG interpretation. The aim of this study is to provide an improved method for ECG recording, establishing reference range values and determine the QT formulas with higher correlation to heart rate (HR). A total of 10 Wistar rats, 10 Swiss mice, 10 C57BL/6 mice and 10 FVB/NJ mice were used in the study. Animals were submitted to anesthesia with isoflurane and ECG recording was performed using a six-channel non-invasive electrocardiograph. QT was corrected using the following formulas: Bazzett, Fridericia, Mitchell, Hodges, Van der Water and Framingham. Normal range values for EC...
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Huntington’s disease (HD) is a neurodegenerative autosomal dominant disorder, characterized by symptoms of involuntary movement of the body, loss of cognitive function, psychiatric disorder, leading inevitably to death. It has been... more
Huntington’s disease (HD) is a neurodegenerative autosomal dominant disorder, characterized by symptoms of involuntary movement of the body, loss of cognitive function, psychiatric disorder, leading inevitably to death. It has been previously described that higher levels of brain expression of Cav1 channels are involved in major neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Our results demonstrate that a bacterial artificial chromosome (BAC)-mediated transgenic mouse model (BACHD mice) at the age of 3 and 12 months exhibits significantly increased Cav1.2 protein levels in the cortex, as compared with wild-type littermates. Importantly, electrophysiological analyses confirm a significant increase in L-type Ca2+ currents and total Ca2+ current density in cortical neurons from BACHD mice. By using an in vitro assay to measure neuronal cell death, we were able to observe neuronal protection against glutamate toxicity after treatment with Cav1 blockers...
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Nerol (C10H18O) is a monoterpene found in many essential oils, such as lemon balm and hop. In this study, we explored the contractile and electrophysiological properties of nerol and demonstrated its antiarrhythmic effects in guinea pig... more
Nerol (C10H18O) is a monoterpene found in many essential oils, such as lemon balm and hop. In this study, we explored the contractile and electrophysiological properties of nerol and demonstrated its antiarrhythmic effects in guinea pig heart preparation. Nerol effects were evaluated on atrial and ventricular tissue contractility, electrocardiogram (ECG), voltage-dependent L-type Ca2+current (ICa,L), and ouabain-triggered arrhythmias. Overall our results revealed that by increasing concentrations of nerol (from 0.001 to 30 mM) there was a significant decrease in left atrium contractile force. This effect was completely and rapidly reversible after washing out (~ 2 min). Nerol (at 3 mM concentration) decreased the left atrium positive inotropic response evoked by adding up CaCl2in the extracellular medium. Interestingly, when using a lower concentration of nerol (30μM), it was not possible to clearly observe any significant ECG signal alterations but a small reduction of ventricular ...
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Huntington's disease (HD) is a neurodegenerative genetic disorder. Although described as a brain pathology, there is evidence suggesting that defects in other systems can contribute to disease progression. In line with this,... more
Huntington's disease (HD) is a neurodegenerative genetic disorder. Although described as a brain pathology, there is evidence suggesting that defects in other systems can contribute to disease progression. In line with this, cardiovascular defects are a major cause of death in HD. To date, relatively little is known about the peripheral abnormalities associated with the disease. Here, we applied a range of assays to evaluate cardiac electro‐mechanical properties in vivo, using a previously characterized mouse model of HD (BACHD), and in vitro, using cardiomyocytes isolated from the same mice. We observed conduction disturbances including QT interval prolongation in BACHD mice, indicative of cardiac dysfunction. Cardiomyocytes from these mice demonstrated cellular electro‐mechanical abnormalities, including a prolonged action potential, arrhythmic contractions, and relaxation disturbances. Cellular arrhythmia was accompanied by an increase in calcium waves and increased Ca2+/calm...
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Little is known regarding the role of the Suppressor of Cytokine Signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of SOCS2 ablation for Leukemia Inhibitory Factor (LIF)-induced... more
Little is known regarding the role of the Suppressor of Cytokine Signaling (SOCS) in the control of cytokine signaling in cardiomyocytes. We investigated the consequences of SOCS2 ablation for Leukemia Inhibitory Factor (LIF)-induced enhancement of intracellular Ca(2+) ([Ca(2+)]i) transient by performing experiments with cardiomyocytes from SOCS2-knockout (ko) mice. Similar levels of SOCS3 transcripts were seen in cardiomyocytes from wild-type and SOCS2-ko, while SOCS1 mRNA was reduced in SOCS2-ko. Immunoprecipitation experiments showed increased SOCS3 association with gp130 receptor in SOCS2-ko myocytes. Measurements of Ca(2+) in wild-type myocytes exposed to LIF showed a significant increase in the magnitude of the Ca(2+) transient. These changes were absent in LIF-treated SOCS2-ko cells. LIF activation of ERK and STAT3 was observed in both wild-type and SOCS2-ko cells, indicating that in SOCS2-ko LIF receptors were functional, despite the lack of effect in the Ca(2+) transient. I...
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RESUMO Introdução: A capacidade intrínseca para o exercício aeróbico está relacionada com o inotropismo cardíaco. Por outro lado, a participação do óxido nítrico (NO) como mensageiro intracelular sobre a dinâmica do Ca2+ ainda permanece... more
RESUMO Introdução: A capacidade intrínseca para o exercício aeróbico está relacionada com o inotropismo cardíaco. Por outro lado, a participação do óxido nítrico (NO) como mensageiro intracelular sobre a dinâmica do Ca2+ ainda permanece desconhecida em ratos com diferentes capacidades intrínsecas para o exercício. Objetivo: Avaliar se o NO modula diferentemente o transiente intracelular de Ca2+ e liberações espontâneas de Ca2+(sparks) em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício. Métodos: Ratos machos Wistar foram selecionados como desempenho padrão (DP) e alto desempenho (AD), de acordo com a capacidade de exercício até a fadiga, mensurada através de teste de esforço progressivo em esteira. Os cardiomiócitos dos ratos foram utilizados para determinar o transiente intracelular de Ca2+ e Ca2+sparks em microscópio confocal. Para estimar a contribuição do NO foi utilizado o inibidor das sínteses do NO (L-NAME, 100 µM). Os dados foram analisados atr...
Research Interests: Physics and Humanities
Nanomaterials can transfect hard-to-transfect cells with efficiency and citotoxicity even better than the ones from some commercial reagents.
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Objectives We studied the effects of ethyl acetate fraction (EAcF) obtained from Erythrina velutina leaves on mammalian myocardium. Methods The effect of EAcF on the contractility was studied using guinea-pig left atria mounted in a... more
Objectives We studied the effects of ethyl acetate fraction (EAcF) obtained from Erythrina velutina leaves on mammalian myocardium. Methods The effect of EAcF on the contractility was studied using guinea-pig left atria mounted in a tissue bath (Tyrode's solution, 29°C, 95% CO2, 5% O2) and electrically stimulated (1 Hz). Concentration-response curves of EAcF were obtained in the presence of propranolol (1 μm), nifedipine (1 μm) and in reserpinized animals (5 mg/kg). The involvement of l-type calcium current (ICa,L) on the EAcF effect was observed in cardiomyocytes of mice assessed using patch-clamp technique. Key findings EAcF (550 μg/ml) had a positive inotropic effect, increasing the atrial force by 164% (EC50 = 157 ± 44 μg/ml, n = 6), but it was less potent than isoproterenol (EC50 = 0.0036 ± 0.0019 μg/ml, n = 8). The response evoked by EAcF was abolished by propranolol or nifedipine. Reserpine did not alter the inotropic response of EAcF. Furthermore, an enhancement of the I...
Research Interests: Chemistry, Calcium, Medicine, Mammals, Pharmacology and Clinical pharmacy, and 15 moreFemale, Animals, Male, Heart, Plant extracts, Myocardium, Muscle contraction, Nifedipine, Catecholamines, Isoproterenol, Contractility, inotrope, Guinea pigs, Pharmacology and pharmaceutical sciences, and Heart atria
The aim of the present study was to evaluate the Ca2+handling and contractility properties of cardiomyocytes isolated from rats with high intrinsic aerobic exercise capacity. Standard-performance (SP) and high-performance (HP) rats were... more
The aim of the present study was to evaluate the Ca2+handling and contractility properties of cardiomyocytes isolated from rats with high intrinsic aerobic exercise capacity. Standard-performance (SP) and high-performance (HP) rats were categorized with a treadmill progressive exercise test according to the exercise time to fatigue (TTF). The SP group included rats with TTF between 16.63 and 46.57 min, and the HP group included rats with TTF >46.57 min. Isolated ventricular cardiomyocytes were dissociated from the hearts of SP and HP rats, and intracellular global Ca2+([Ca2+]i) transients were measured. The [Ca2+]itransient peak was increased in the HP group relative to the SP group (5.54 ± 0.31 vs. 4.18 ± 0.12 F/F0; P ≤ 0.05) and was positively correlated with the TTF attained during the progressive test ( r = 0.81). We also performed contractility measurements in isolated cardiomyocytes and found higher amplitude of contraction in the HP group compared with the SP group (6.7 ± ...
Research Interests: Endocrinology, Chemistry, Kinetics, Calcium, Confocal Microscopy, and 15 moreMedicine, Biological Sciences, Internal Medicine, Applied, Animals, Male, Calcium Signaling, Applied Physiology, Muscle Fatigue, Calcium Binding Proteins, Heart Ventricles, Exercise Tolerance, Contractility, Medical and Health Sciences, and exercise capacity
High serum levels of aldosterone have been linked to the development of cardiac disease. In contrast, angiotensin (Ang)-(1-7) was extensively shown to possess cardioprotective effects, including the attenuation of cardiac dysfunction... more
High serum levels of aldosterone have been linked to the development of cardiac disease. In contrast, angiotensin (Ang)-(1-7) was extensively shown to possess cardioprotective effects, including the attenuation of cardiac dysfunction induced by excessive mineralocorticoid activation in vivo, suggesting possible interactions between these 2 molecules. Here, we investigated whether there is cross-talk between aldosterone and Ang-(1-7) and its functional consequences for calcium (Ca 2+ ) signaling in ventricular myocytes. Short-term effects of aldosterone on Ca 2+ transient were assessed in Fluo-4/AM-loaded myocytes. Confocal images showed that Ang-(1-7) had no effect on Ca 2+ transient parameters, whereas aldosterone increased the magnitude of the Ca 2+ transient. Quite unexpectedly, addition of Ang-(1-7) to aldosterone-treated myocytes further enhanced the amplitude of the Ca 2+ transient suggesting a synergistic effect of these molecules. Aldosterone action on Ca 2+ transient amplit...
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Thiamine is an important cofactor of metabolic enzymes, and its deficiency leads to cardiovascular dysfunction. First, we characterized the metabolic status measuring resting oxygen consumption rate and lactate blood concentration after... more
Thiamine is an important cofactor of metabolic enzymes, and its deficiency leads to cardiovascular dysfunction. First, we characterized the metabolic status measuring resting oxygen consumption rate and lactate blood concentration after 35 days of thiamine deficiency (TD). The results pointed to a decrease in resting oxygen consumption and a twofold increase in blood lactate. Confocal microscopy showed that intracellular superoxide (∼40%) and H2O2(2.5 times) contents had been increased. In addition, biochemical activities and protein expression of SOD, glutathione peroxidase, and catalase were evaluated in hearts isolated from rats submitted to thiamine deprivation. No difference in SOD activity was detected, but protein levels were found to be increased. Catalase activity increased 2.1 times in TD hearts. The observed gain in activity was attended by an increased catalase protein level. However, a marked decrease in glutathione peroxidase activity (control 435.3 ± 28.6 vs. TD 199.4...
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Background Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of... more
Background Chagas disease (CD) is a neglected disease that induces heart failure and arrhythmias in approximately 30% of patients during the chronic phase of the disease. Despite major efforts to understand the cellular pathophysiology of CD there are still relevant open questions to be addressed. In the present investigation we aimed to evaluate the contribution of the Na+/Ca2+ exchanger (NCX) in the electrical remodeling of isolated cardiomyocytes from an experimental murine model of chronic CD. Methodology/Principal findings Male C57BL/6 mice were infected with Colombian strain of Trypanosoma cruzi. Experiments were conducted in isolated left ventricular cardiomyocytes from mice 180–200 days post-infection and with age-matched controls. Whole-cell patch-clamp technique was used to measure cellular excitability and Real-time PCR for parasite detection. In current-clamp experiments, we found that action potential (AP) repolarization was prolonged in cardiomyocytes from chagasic mic...
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The scientific interest in (+)-usnic acid has grown because of its antitumor, cytotoxic, and antimicrobial activities as well as weight loss. However, overuse of usnic acid has been related with severe hepatotoxicity, making its use... more
The scientific interest in (+)-usnic acid has grown because of its antitumor, cytotoxic, and antimicrobial activities as well as weight loss. However, overuse of usnic acid has been related with severe hepatotoxicity, making its use questionable. In this study, we decided to expand the knowledge of usnic acid biological activities by characterizing its effects on the mammalian myocardium as a potential pharmacological target. Usnic acid was isolated from samples of Cladonia substellata and submitted to chemical characterization. Molecular inclusion complexes of usnic acid with hydroxypropyl β-cyclodextrin were prepared to improve its water solubility. The effects of usnic acid on the atrial contractility and Ca2+ influx were carried out in the left atrium of guinea pigs and the effect of usnic acid on the L-type Ca2+ current was performed in rat ventricular cardiomyocytes enzymatically isolated. To evaluate the membrane integrity of cells subjected to usnic acid, we used histologica...
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The TTX-sensitive Ca(2+) current [I(Ca(TTX))] observed in cardiac myocytes under Na(+)-free conditions was investigated using patch-clamp and Ca(2+)-imaging methods. Cs(+) and Ca(2+) were found to contribute to I(Ca(TTX)), but TEA(+) and... more
The TTX-sensitive Ca(2+) current [I(Ca(TTX))] observed in cardiac myocytes under Na(+)-free conditions was investigated using patch-clamp and Ca(2+)-imaging methods. Cs(+) and Ca(2+) were found to contribute to I(Ca(TTX)), but TEA(+) and N-methyl-D-glucamine (NMDG(+)) did not. HEK-293 cells transfected with cardiac Na(+) channels exhibited a current that resembled I(Ca(TTX)) in cardiac myocytes with regard to voltage dependence, inactivation kinetics, and ion selectivity, suggesting that the cardiac Na(+) channel itself gives rise to I(Ca(TTX)). Furthermore, repeated activation of I(Ca(TTX)) led to a 60% increase in intracellular Ca(2+) concentration, confirming Ca(2+) entry through this current. Ba(2+) permeation of I(Ca(TTX)), reported by others, did not occur in rat myocytes or in HEK-293 cells expressing cardiac Na(+) channels under our experimental conditions. The report of block of I(Ca(TTX)) in guinea pig heart by mibefradil (10 microM) was supported in transfected HEK-293 ce...
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Research Interests: Mass Spectrometry, Medicine, Western blotting, Animals, Male, and 12 moreResistance Training, Endocannabinoid System, Clinical Sciences, High Pressure Liquid Chromatography, Fluorescent Antibody Technique, Rats, Periaqueductal Gray, Nociception, Wistar Rats, Endocannabinoids, Neurosciences, and Pain Measurement
Research Interests: Microscopy, Biology, Calcium, Confocal Microscopy, Medicine, and 15 moreMice, Female, Animals, Male, Heart, Functional impairment, Animal Model, Creatine Kinase, Recombinant DNA, Myocardium, Monoclonal Antibody, Enzyme Linked Immunosorbent Assay, Antigens, Pharmacology and pharmaceutical sciences, and In Vitro Techniques
Essential oils are natural, complex and multi-component systems composed mainly of terpenes in addition to some other non-terpenes compounds that are widely used to prevent and treat human diseases. (-)-alpha-Bisabolol is an unsaturated... more
Essential oils are natural, complex and multi-component systems composed mainly of terpenes in addition to some other non-terpenes compounds that are widely used to prevent and treat human diseases. (-)-alpha-Bisabolol is an unsaturated monocyclic sesquiterpene alcohol found as the major constituent of many essential oils, like the German chamomile (Chamomilla recutita (L.) Rauschert), a plant reported to reduce the perception of acute pain and used for centuries for their medicinal properties. Recently, our group demonstrated the antinociceptive-like effect promoted by other terpenes could be associated with the decreased peripheral nerve excitability. Therefore, this study investigated the pharmacological activities of (-)-alpha-bisabolol on mice peripheral nervous system observing the changes on the compound action potential (CAP) characteristics. Using modified single sucrose-gap method in mice sciatic nerves, we acquired CAP recordings in the absence and presence of (-)-alpha-bisabolol (0.5, 1, 5 and 10mM). We observed that this sesquiterpene was able to reduce the neuronal excitability in a concentration-dependent manner, although, such effects were not reversed when the nerve was submitted to wash out. Assessing CAP parameters of depolarization and repolarization, we noticed similarities between (-)-alpha-bisabolol and lidocaine but not with 4-aminopyridine that are considered good blockers for sodium and potassium voltage-gated channels, respectively. Additionally, we also characterized the non-use-dependent profile of (-)-alpha-bisabolol action, in contrast to lidocaine. Thus, we suggested that decreased nervous excitability elicited by (-)-alpha-bisabolol might be caused by an irreversible blockade of voltage-dependent sodium channels.
Research Interests: Pharmacology, Cognitive Science, Chemistry, Electrophysiology, Medicine, and 15 moreEssential Oil, Mice, Female, Animals, Peripheral Nervous System, Potassium, Lidocaine, Peripheral Nerve, Action potential, Aminopyridine, Human Disease, Action Potentials, Neurosciences, Analgesics, and In Vitro Techniques
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In this study we investigated the effects of the genetic deletion of the angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in the mouse heart was evaluated by binding of rhodamine-labeled Ang-(1-7). Cardiac... more
In this study we investigated the effects of the genetic deletion of the angiotensin (Ang)-(1-7) receptor Mas on heart function. Localization of Mas in the mouse heart was evaluated by binding of rhodamine-labeled Ang-(1-7). Cardiac function was examined using isolated heart preparations. Echocardiography was used to confirm the results obtained with isolated heart studies. To elucidate the possible mechanisms involved in the cardiac phenotype observed in Mas −/− mice, whole-cell calcium currents in cardiomyocytes and the expression of collagen types I, III, and VI and fibronectin were analyzed. Ang-(1-7) binding showed that Mas is localized in cardiomyocytes of the mouse heart. Isolated heart techniques revealed that Mas-deficient mice present a lower systolic tension (average: 1.4±0.09 versus 2.1±0.03 g in Mas +/+ mice), ±dT/dt, and heart rate. A significantly higher coronary vessel resistance was also observed in Mas-deficient mice. Echocardiography revealed that hearts of Mas-de...
Research Interests: Endocrinology, Genetics, Electrophysiology, Extracellular Matrix, Echocardiography, and 15 moreHeart Failure, Internal Medicine, Hypertension, Collagen, Animals, Calcium channels, Heart rate, Heart, Clinical Sciences, Angiotensin II, Cardiac function, Diastole, Cardiovascular medicine and haematology, In Vitro Techniques, and Coronary Vessels
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Research Interests: Chemistry, Electrophysiology, Kinetics, Biology, Medicine, and 15 moreIon Channels, Glutamate, Neuropeptides, Animals, Peptides, Peptide, Amino Acid Sequence, Base Sequence, Molecular Identification, Electric Conductivity, Neurosciences, Biochemistry and cell biology, Molecular Sequence Data, Nucleotide sequence, and Pharmacology and pharmaceutical sciences
Research Interests: Physiology, Chemistry, Calcium, Medicine, Glibenclamide, and 15 moreAnimals, Male, Vascular endothelium, Potassium, Alkaloids, Medical Physiology, Norepinephrine, Rats, Potassium Channels, Tetraethylammonium, Alkaloid, Vasodilatation, Vascular Smooth Muscle, Muscle cells, and Pharmacology and pharmaceutical sciences
Research Interests: Endocrinology, Calcium, Type 2 Diabetes, Medicine, Patch-clamp and imaging techniques, and 15 moreSignal Transduction, Mice, Animals, Male, Vasoconstriction, Mouse Model, Muscle contraction, Type 2 Diabetes Mellitus, Experimental Diabetes Mellitus Type 1 and 2, Phenylephrine, Aorta, Vasodilation, Contractility, Phosphatidylinositol 3-KINASE, and Pharmacology and pharmaceutical sciences
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The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest... more
The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it represents part of the primary structure of the toxin δ-CNTX-Pn1c (PnTx2-6), isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests suggest that PnPP-19 induces antinociception by activation of CB1, μ and δ opioid receptors. Since the peripheral and central antinociception induced by PnPP-19 involves opioid activation, the aim of this work was to identify whether this synthetic peptide could directly activate opioid receptors and investigate the subtype selectivity for μ-, δ- and/or κ-opioid receptors. Furthermore, we also studied the modulation of calcium influx driven by PnPP-19 in dorsal root ganglion neurons, and analyzed whether this modulation was opioid-mediated. PnPP-19 selectively activates μ-opioid receptors inducing indirectly inhibition of calcium channels and hereby impairing calcium influx in dorsal root ganglion (DRG) neurons. Interestingly, notwithstanding the activation ...
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B1- and B2-kinin receptors are G protein-coupled receptors that play an important role in the vascular function. Therefore, the present study was designed to evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced... more
B1- and B2-kinin receptors are G protein-coupled receptors that play an important role in the vascular function. Therefore, the present study was designed to evaluate the participation of kinin receptors in the acetylcholine (ACh)-induced vascular relaxation, focusing on the protein-protein interaction involving kinin receptors with endothelial and neuronal nitric oxide synthases (eNOS and nNOS). Vascular reactivity, nitric oxide (NO·) and reactive oxygen species (ROS) generation, co-immunoprecipitation were assessed in thoracic aorta from male wild-type (WT), B1- (B1R(-/-)), B2- (B2R(-/-)) knockout mice. Some vascular reactivity experiments were also performed in a double kinin receptors knockout mice (B1B2R(-/-)). For pharmacological studies, selective B1- and B2-kinin receptors antagonists, NOS inhibitors and superoxide dismutase (SOD) mimetic were used. First, we show that B1- and B2-kinin receptors form heteromers with nNOS and eNOS in thoracic aorta. To investigate the functio...
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Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection.... more
Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase cha...
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Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades... more
Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. Immunodetection of T. cruzi antigen TcRBP28 was observed in endothelial cells. There was a decreased endothelial nitric oxide synthase (eNOS)-derived NO-dependent vascular relaxation, and increased vascular contractility accompanied by augmented superoxide anions production. Endothelial removal, inhibition of cyclooxygenase 2 (COX-2), blockade of thromboxane A2 (TXA2) TP receptors, and scavenger of superoxide normalized the contractile response. COX-2, thromboxane synthase, inducible nitric oxide synthase (iNOS), p65 NFκB subunit and p22(phox) of NAD(P)H oxidase (NOX) subunit expressions were increased in vessels of chagasic animals. Serum TNF-α was augmented. Basal...
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In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these... more
In this study, our aims were to investigate transient receptor potential melastatin-8 channels (TRPM8) involvement in rotundifolone induced relaxation in the mesenteric artery and to increase the understanding of the role of these thermosensitive TRP channels in vascular tissue. Thus, message and protein levels of TRPM8 were measured by semi-quantitative PCR and western blotting in superior mesenteric arteries from 12 week-old Spague-Dawley (SD) rats. Isometric tension recordings evaluated the relaxant response in mesenteric rings were also performed. Additionally, the intracellular Ca2+ changes in mesenteric artery myocytes were measured using confocal microscopy. Using PCR and western blotting, both TRPM8 channel mRNA and protein expression was measured in SD rat mesenteric artery. Rotundifolone and menthol induced relaxation in the isolated superior mesenteric artery from SD rats and improved the relaxant response induced by cool temperatures. Also, this monoterpene induced an in...