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Diabetes mellitus (DM) is a chronic disease characterized by persistent hyperglycemia, which is a major contributing factor to chronic kidney disease (CKD), end-stage renal disease (ESRD), and cardiovascular-related deaths. There are several mechanisms leading to kidney injury, with hyperglycemia well known to stimulate oxidative stress, inflammation, tissue remodeling, and dysfunction in the vascular system and organs. Increased reactive oxygen species (ROS) decrease the bioavailability of vasodilators while increasing vasoconstrictors, resulting in an imbalance in vascular tone and the development of hypertension. Treatments for diabetes focus on controlling blood glucose levels, but due to the complexity of the disease, multiple drugs are often required to successfully delay the development of microvascular complications, including CKD. In this context, naringenin, a flavonoid found in citrus fruits, has demonstrated anti-inflammatory, anti-fibrotic, and antioxidant effects, suggesting its potential to protect the kidney from deleterious effects of diabetes. This review aims to summarize the scientific evidence of the effects of naringenin as a potential therapeutic option for diabetes-induced CKD.
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The mechanism is unclear for the reported protective effect of hyperbaric oxygen preconditioning against oxidative stress in tissues, and the distinct effects of hyperbaric oxygen applied after stress. The trained mice were divided into three groups: the control, hyperbaric oxygenation preconditioning, and hyperbaric oxygenation applied after mild (fasting) or hard (prolonged exercise) stress. After preconditioning, we observed a decrease in basal levels of nitric oxide, tetrahydrobiopterin, and catalase despite the drastic increase in inducible and endothelial nitric oxide synthases. Moreover, the basal levels of glutathione, related enzymes, and nitrosative stress only increased in the preconditioning group. The control and preconditioning groups showed a similar mild stress response of the endothelial and neuronal nitric oxide synthases. At the same time, the activity of all nitric oxide synthase, glutathione (GSH) in muscle, declined in the experimental groups but increased in control during hard stress. The results suggested that hyperbaric oxygen preconditioning provoked uncoupling of nitric oxide synthases and the elevated levels of GSH in muscle during this study, while hyperbaric oxygen applied after stress showed a lower level of GSH but higher recovery post-exercise levels in the majority of antioxidant enzymes. We discuss the possible mechanisms of the redox response and the role of the nitric oxide in this process.
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Objectives: Spiders of the Loxosceles genus, known as violin spiders, produce venom with dermonecrotic and systemic effects, as it is a species widely distributed in the world, its study represents a high medical relevance. Systemic loxoscelism, which occurs in 1 in 5 cases and is the most frequent in children, can be fatal, so the study of effective therapy is of great relevance. In the present study, we compared different therapeutic options to mitigate the systemic effects of Loxosceles boneti venom in a model in which prepubertal rats were used. Materials and Methods: A model of systemic intoxication by L. boneti venom was provoked in male Wistar rats. Study groups were formed: healthy control, with venom and untreated control, treatment with N-acetylcysteine, and/or hyperbaric oxygenation therapy. Subsequently, pathological analysis of the kidney and lung was performed. The oxidant-antioxidant response was evaluated, and molecular analysis of the COX-1 and COX-2 enzymes was performed. Results: Regenerative changes were observed at the cellular level in both treatments, being more noticeable in the hyperbaric oxygen therapy (HBO) group. The anti-oxidant response was outstanding in the same group. Conclusion: Both treatments offer considerable benefits, however; further studies are needed to provide adequate therapeutics.
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BACKGROUND: The estimation of left ventricular ejection fraction (LVEF) by 2D echocardiography (2D-ECHO) is the most used tool to assess LV systolic function (LVSF). Global longitudinal strain (GLS) has recently been suggested as a superior method for several evaluations. This study explored the association and prevalence of LV systolic dysfunction (LVSD) by using these methods in patients with end-stage renal disease (ESRD) and severe hyperparathyroidism (SHPTH); both associated with cardiovascular events (CEs). AIM: To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO. METHODS: In 62 patients with ESRD and SHPTH, asymptomatic, and without a history of CEs, LVSF was evaluated by 2D-ECHO, obtaining the EF, by the Simpson biplane method, and GLS by speckle tracking. RESULTS: The total patients with ESRD had a preserved LVEF (> 50%) but abnormal GLS (< 13.55%). Additionally, multivariate analysis showed an independent association of GLS and serum parathyroid hormone (PTH), LV mass index, and hemoglobin. Also, PTH was independently associated with lateral e' wave and tricuspid regurgitation velocity. CONCLUSION: In patients with SHPTH linked to ESRD, the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.
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Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional damage to ischemic myocardial tissue; this forces to seek therapies of cardioprotection to reduce this additional damage. There are many cardioprotective agents; within these, cannabinoids have shown to have beneficial effects, mainly cannabidiol (CBD). CBD is a non psychoactive cannabinoid. To evaluate the effect in experimental models of CBD in myocardial ischemia reperfusion in rats, twelve-week-old male rats have been used. The animals were divides in 3 groups: control(C), ischemia reperfusion (IR) and CBD pretreatment (1/day/5mg/kg /10days). Langendorff organ isolate studies were performed, and the area of infarction was assessed with triphenyl tetrazolium, in addition to molecular analysis of AT1 and AT2 receptors and Akt and Erk proteins and their phosphorylated forms related to RISK pathways. It was observed that there is an improvement with the use of CBD increasing inotropism and cardiac lusitropism, improving considerably the cardiovascular functionality. These could be related to the reduction of the area of infarction and activation of the AT2 receptor and the RISK pathway with absence of activation of the AT2 receptor (these could relate the reduction of the infarct area and the restoration of cardiovascular function with the activation of the AT2 receptor and the RISK pathway with the absence of activation of the AT2 receptor). The use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.
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Canabidiol/uso terapêutico , Cardiotônicos/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Canabidiol/farmacologia , Cardiotônicos/farmacologia , Coração/fisiologia , Hemodinâmica , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/metabolismo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
OBJECTIVE: In the pathogenesis of pterygium, the protective role of glutathione and nitric oxide production is unclear. These are important factors for homeostasis in the redox state of cells. The aim of this study was to determine the levels of these and related parameters in pterygium tissue. Patients and Methods. The study sample consisted of 120 patients diagnosed with primary or recurrent pterygium. Five groups of tissue samples were examined: control, primary pterygium, recurrent pterygium, and two groups of primary pterygium given a one-month NAC presurgery treatment (topical or systemic). The levels of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), 3-nitrotyrosine (3NT), reduced and oxidized glutathione (GSH and GSSG), and catalase (CAT) were evaluated in tissue homogenates. RESULTS: Compared with the control, decreased levels of eNOS, NO, and 3-nitrotyrosine as well as the degree of oxidation of GSH (GSSG%) were observed in primary and recurrent pterygium. 3-Nitrotyrosine and GSSG% were reduced in the other pterygium groups. GSH and CAT were enhanced in recurrent pterygium and systemic-treated primary pterygium but were unchanged for topical-treated primary pterygium. There was a strong positive correlation of eNOS with NO and 3NT, GSSG% with NO and 3NT, and GSH with GSSG and CAT. Women showed a higher level of GSH and catalase in primary pterygium, whereas a lower level of GSH and a higher level of NO in recurrent pterygium. CONCLUSION: The results are congruent with the following proposed sequence of events leading to a protective response of the organism during the pathogenesis of primary pterygium: a decreased level of eNOS provokes a decline in the level of NO in pterygium tissue, which then leads to reduced S-nitrosylation of GSH or other thiols and possibly to the modulation of the intracellular level of GSH through synthesis and/or mobilization from other tissues.
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Oxidative stress is involved in the development of diabetes. Nitric oxide (NO) contributes to oxidative stress, affects the synthesis of glutathione (GSH) in tissues and also regulates important physiological processes. The levels of nitrosative stress, assessed by measuring the levels of 3-nitrotirosina (3NT) as well as the bioavailability of NO are modulated by exercise and hyperbaric oxygenation (HBO). The aim of the present study was to evaluate the effects of exercise and HBO on the levels of NO, 3NT and GSH in tissues of various organs obtained from diabetic mice. Female mice were fed a high-fat/high-fructose diet to induce diabetes. Mice with diabetes were subjected to exercise and/or HBO. Initial and final concentrations of NO, 3NT and GSH were assessed in the muscle, liver, kidney, heart, spleen, lung, brain, visceral adipose, thoracic aorta and small intestine. Diabetes did not affect initial values of NO, although it significantly increased the levels of 3NT. The basal level of GSH in the diabetic group was lower than or comparable to that of the control group in the majority of the organs assessed. A negative correlation was observed between 3NT and GSH levels in the initial values of all tissues of the control group only, whereas all pathological tissues showed a positive correlation between NO and GSH. There was an increase or a stabilization of GSH levels in the majority of the organs in all treated mice despite the increase in nitrosative stress.
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BACKGROUND: The diagnosis of asthma is confirmed with a spirometry: FEV1 ratio (forced expiratory volume in one second)/FVC (forced vital capacity) <80% with reversibility (FEV1 >12% or 200 mL) after using salbutamol. The peak expiratory flow is cheap and easy to use; it measures the forced expiratory flow, of which reversibility > 20% suggests asthma. OBJECTIVE: To know the sensitivity, specificity, and the positive and negative predictive values of the flowmeter. METHODS: A cross-sectional, observational, comparative study. Individuals aged >18 years without contraindications for spirometry were included. They underwent spirometry and peak expiratory flow, and the ACT (Asthma Control Test) questionnaire was applied to them. Sensitivity, specificity, positive predictive value and negative predictive value of the flowmetry were calculated. ROC curve was carried out in order to know the cut-off point of greater sensitivity and specificity. RESULTS: Of 150 patients, 66% were male; the median age was 38 years. According to the guidelines of GINA 2018 (Global Initiative for Asthma); 58.7% were controlled. The sensitivity of the peak expiratory flow was 47%, and the specificity was 87%, with a positive predictive value of 54.8% and a negative predictive value of 84%. The peak expiratory flow showed higher specificity with FEV1 <59%. The cut-off point of greater sensitivity and specificity was a reversibility of 8%, with an area under the curve of 0.70. CONCLUSIONS: The flowmeter has got greater sensitivity in airway obstructions; it is useful when a spirometer is not available.
Antecedentes: El diagnóstico de asma se confirma con espirometría: VEF1 (volumen espiratorio forzado del primer segundo)/CVF (capacidad vital forzada) < 80 %, con reversibilidad (VEF1 >12 % o 200 mL) tras utilizar salbutamol. El flujómetro es barato y fácil de utilizar, mide el flujo espiratorio forzado, cuya reversibilidad > 20 % sugiere asma. Objetivo: Conocer sensibilidad, especificidad y valores predictivos positivos y negativo del flujómetro. Métodos: Estudio transversal, observacional, comparativo. Se incluyó a individuos > 18 años sin contraindicaciones para espirometría, quienes fueron sometidos a espirometría y flujometría y se les aplicó el Asthma Control Test. Se calculó sensibilidad, especificidad y valores predictivos positivo y negativo de la flujometría. Se realizó curva ROC para conocer el punto de corte de mayor sensibilidad y especificidad. Resultados: De 150 pacientes, 66 % fue del sexo masculino; la mediana de edad fue de 38 años. Conforme los criterios de Global Initiative for Asthma 2018, 58.7 % estaba controlado. La sensibilidad de la flujometría fue de 47 %, la especificidad de 87 %, valor predictivo positivo de 54.8 % y negativo de 84 %. La flujometría mostró mayor especificidad con VEF1 < 59 %. El punto de corte de mayor sensibilidad y especificidad fue una reversibilidad de 8 %, con área bajo la curva de 0.70. Conclusiones: El flujómetro tiene mayor sensibilidad en obstrucciones de vía aérea; es de utilidad cuando no se cuenta con un espirómetro.
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Asma/diagnóstico , Asma/fisiopatologia , Pico do Fluxo Expiratório , Espirometria , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
Vascular reactivity can be influenced by the vascular region, animal age, and pathologies present. Prostaglandins (produced by COX-1 and COX-2) play an important role in the contractile response to phenylephrine in the abdominal aorta of young rats. Although these COXs are found in many tissues, their distribution and role in vascular reactivity are not clear. At a vascular level, they take part in the homeostasis functions involved in many physiological and pathologic processes (e.g., arterial pressure and inflammatory processes). The aim of this study was to analyze changes in the contractile response to phenylephrine of thoracic/abdominal aorta and the coronary artery during aging in rats. Three groups of rats were formed and sacrificed at three distinct ages: prepubescent, young and old adult. The results suggest that there is a higher participation of prostanoids in the contractile effect of phenylephrine in pre-pubescent rats, and a lower participation of the same in old rats. Contrarily, there seems to be a higher participation of prostanoids in the contractile response of the coronary artery of older than pre-pubescent rats. Considering that the changes in the expression of COX-2 were similar for the three age groups and the two tissues tested, and that expression of COX-1 is apparently greater in older rats, COX-1 and COX-2 may lose functionality in relation to their corresponding receptors during aging in rats.
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This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression.
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Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Ácidos Sulfínicos/uso terapêutico , Animais , Antioxidantes/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dissulfetos , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipertensão/complicações , Hipertensão/metabolismo , Rim/efeitos dos fármacos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Perfusão , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Ácidos Sulfínicos/farmacologia , Sístole/efeitos dos fármacosRESUMO
Mechanisms underlying age-dependent changes in vasodilator responses to beta-adrenergic drugs are poorly understood. The aim of the current study was to compare responses to isoproterenol (a non-selective beta-adrenergic receptor agonist) in phenylephrine or KCl precontracted aortic rings from 3 week and 3 month old male Wistar rats. Both the mechanism and the subtype of beta-adrenergic receptor underlying the response to isoproterenol in the both age groups were examined. Endothelial removal, pre-contraction with KCl (40 mM), pre-treatment with tetraethylammonium or with N(omega)-Nitro-L-arginine methyl ester inhibited the vasodilator response to isoproterenol only in aortic rings from older rats. The inhibition was total when TEA and L-NAME were administered together. In both age groups the response to isoproterenol was unaffected by the beta1-adrenergic antagonist CGP20712A, but was significantly inhibited by ICI 118551 (a beta2-adrenergic-antagonist) and to a greater extent by SR 59230A (a non-selective beta 3-adrenergic antagonist), the inhibition being more evident in the older rats. Unlike younger rats, in older animals the response to isoproterenol was partially dependent on endothelial nitric oxide and on K+ channels. In both age groups, beta2- and beta3-, but not beta1-adrenergic receptors were involved. The degree of relative participation of beta2 and beta3 adrenergic receptors may change with age and explain the differences in response to isoproterenol.
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Aorta/efeitos dos fármacos , Receptores Adrenérgicos beta/fisiologia , Vasodilatação/efeitos dos fármacos , Fatores Etários , Animais , Aorta/fisiologia , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Wistar , Compostos de Tetraetilamônio/farmacologiaRESUMO
Prostanoids are involved in the phenylephrine-induced contraction of the aorta. Here, we examined whether or not constitutive cyclooxygenase-2 (phosholipases C and A2) is the source of prostanoids in the smooth muscle of the arterial wall of the thoracic and abdominal aorta. Both cyclooxygenase isoforms (COX-1 and COX-2) were expressed in the two aortic segments, but their expression was not altered by phenylephrine, the protein synthesis inhibitor cycloheximide, or the phospholipase A2 inhibitors arachidonyl trifluoromethyl ketone and methyl arachidonyl fluorophosponate. Indomethacin and NS398, which are a non-selective and selective COX-2 inhibitor, respectively, but not SC-560, which is a COX-1-selective inhibitor, inhibited the effect of phenylephrine on the abdominal, but not the thoracic, aorta. Similarly, U73122, which is a phospholipase C inhibitor, and RHC80267, which is a diacylglycerol lipase inhibitor, inhibited the effect of phenylephrine. These findings suggest that prostanoids, which are produced by constitutively active COX-2, influence the contractile response of the abdominal aorta and that the production of arachidonic acid relies on phospholipase C and diacylglycerol lipase.
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Aorta Abdominal/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/fisiologia , Cicloeximida/farmacologia , Inibidores de Ciclo-Oxigenase/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Immunoblotting , Indometacina/metabolismo , Indometacina/farmacologia , Contração Muscular/fisiologia , Músculo Liso/metabolismo , Músculo Liso/fisiologia , Nitrobenzenos/metabolismo , Nitrobenzenos/farmacologia , Fenilefrina/farmacologia , Inibidores de Fosfolipase A2 , Pirazóis/metabolismo , Pirazóis/farmacologia , Ratos , Sulfonamidas/metabolismo , Sulfonamidas/farmacologia , Fosfolipases Tipo C/metabolismoRESUMO
Several of the luminal endothelial glycocalyx functions are exerted via interactions with glycosidic components and sugar binding proteins with lectinic activity. One important example is the mannose receptor (MR). The MR has been detected in cell types that mediate the phagocytosis and pinocytosis of particles and solutes containing mannose. Using isolated constant pressurized rat mesenteric arteries (RMA), we evaluated the effects of a mannose polymer in the vascular tone. RMA were pre-contracted with 10 micromol/L phenylephrine and carbohydrates were perfused at 20 microliters/min. Perfusion of free D-mannose (1 nmol/L to 100 micromol/L) induced a concentration-dependent vasodilation of pre-contracted RMA. Perfusion of mannose polymer (1 nmol/L to 100 micromol/L) induced a larger effect in a concentration-dependent vasodilation. Mannose polymer's maximum effect reached a 96 percent of basal diameter; this significant vasodilation was not nitric oxide (NO) or cyclooxygenase (COX) dependent effect. We corroborated the binding of the mannose polymer to the endothelial lumen, by perfusion of a fluorescently labeled mannose polymer; and also, we detected a significant level of MR mRNA in whole mesenteric arteries. With all these, we proposed a novel effect of a MR in the regulation of vascular tone.
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Endotélio Vascular/fisiologia , Lectinas Tipo C/fisiologia , Mananas/farmacologia , Lectinas de Ligação a Manose/fisiologia , Artérias Mesentéricas/fisiologia , Receptores de Superfície Celular/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Endotélio Vascular/efeitos dos fármacos , Lectinas Tipo C/genética , Masculino , Mananas/síntese química , Manose/antagonistas & inibidores , Manose/farmacologia , Receptor de Manose , Lectinas de Ligação a Manose/genética , Artérias Mesentéricas/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores de Superfície Celular/genética , Vasodilatadores/farmacologiaRESUMO
Putrescine, spermidine and spermine are natural compounds found in up to millimolar concentrations in eukaryotic and prokaryotic cells. At physiologic pH, the polyamines are protonated (+2, +3 and +4 charges), their polycationic properties lead to the assumption that they could affect physiological systems by binding to anionic sites of the cellular membrane and/or by modulating ion channels. At the cardiovascular level, their effects are not completely understood. However, these compounds may be able to exert the induction of synthesis and release of cellular mediators. In an attempt to explore this possibility, we used the isolated and perfused rat heart, Langendorff, model in order to evaluate the inotropic effects of these polyamines, putrescine, spermidine and spermine. Dose-response curves (0.1-0.6 mM) for putrescine, spermidine and spermine were constructed; with the finding that spermine had the largest negative effect. The obtained effects were not blocked by nitric oxide synthesis inhibitors (L-NAME), H(1) and H(2) receptor antagonists (Brompheniramine and Cimetidine) or by Glibenclamide, an antagonist of ATP-sensitive K(+) channels. We found that spermine-induced and increased ATP concentration in cardiac effluents. Reactive Blue, a P(2y) purinoreceptor antagonist and Aminophylline, an unspecific adenosine receptor antagonist, blocked the spermine-induced effects. These results showed that ATP, at least in part, is responsible of the spermine cardiovascular effects. Adenosine was shown to also play an important role on those effects.
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Trifosfato de Adenosina/metabolismo , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Espermina/farmacologia , Animais , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Poliaminas/farmacologia , Antagonistas de Receptores Purinérgicos P1 , Antagonistas do Receptor Purinérgico P2 , Purinas/metabolismo , Ratos , Ratos WistarRESUMO
Sex steroids have been associated with cardiovascular diseases and the modification of the risk of coronary artery disease (CAD). We cultured aortic endothelial cells from young adult male rats and loaded them with Fura 2 in order to evaluate the direct effects of testosterone on endothelial cells and the probable regulation of bradykinin-induced effects on intracellular calcium ([Ca(2+)](i)) kinetics, effects that are mediated through an increase in intracellular [IP(3)], which in turn stimulates the rapid release of Ca(2+) from ER stores. Our results show that testosterone had no direct effects on [Ca(2+)](i) kinetics, but did block bradykinin-induced increases in intracellular calcium concentration in endothelial cells. This effect was concentration-dependent; the steroid was applied only 30 s before bradykinin application and thus, the effect can be considered nongenomic in origin. Membrane localization of a putative androgen receptor in endothelial cells could be responsible for this effect. In summary, testosterone can modulate the effects induced by activation of membrane-bound bradykinin receptors.