d-Limonene complexed with cyclodextrin attenuates cardiac arrhythmias in an experimental model of doxorubicin-induced cardiotoxicity: Possible involvement of calcium/calmodulin-dependent protein kinase type II.

BACKGROUND: Arrhythmias are one manifestation of the cardiotoxicity that results from doxorubicin (Doxo) administration. Although cardiotoxicity is an anticipated outcome in anticancer therapies, there is still a lack of treatment options available for its effective management. This study sought to evaluate the possible cardioprotective effect of complex d-limonene (DL) plus hydroxypropyl-ß-cyclodextrin (HßDL) during treatment with Doxo, focusing on the arrhythmic feature. METHODS: Cardiotoxicity was induced in Swiss mice with Doxo 20 mg/kg, with 10 mg/kg of HßDL being administered 30 min before the Doxo. Plasma CK-MB and LDH levels were analyzed. Cellular excitability and susceptibility to cardiac and cardiomyocyte arrhythmias were evaluated using in vivo (pharmacological cardiac stress) and in vitro (burst pacing) ECG protocols. Ca2+ dynamics were also investigated. The expression of CaMKII and its activation by phosphorylation and oxidation were evaluated by western blot, and molecular docking was used to analyze the possible interaction between DL and CaMKII. RESULTS: Electrocardiograms showed that administration of 10 mg/kg of HßDL prevented Doxo-induced widening of the QRS complex and QT interval. HßDL also prevented cardiomyocyte electrophysiological changes that trigger cellular arrhythmias, such as increases in action potential duration and variability; decreased the occurrence of delayed afterdepolarizations (DADs) and triggered activities (TAs), and reduced the incidence of arrhythmia in vivo. Ca2+ waves and CaMKII overactivation caused by phosphorylation and oxidation were also decreased. In the in silico study, DL showed potential inhibitory interaction with CaMKII. CONCLUSION: Our results show that 10 mg/kg of ßDL protects the heart against Doxo-induced cardiotoxicity arrhythmias, and that this is probably due to its inhibitory effect on CaMKII hyperactivation.

Phytochemical screening and cardiovascular effects of the ethanol extract of Erythroxylum passerinum mart.

Species of Erythroxylum genus are popularly used as anti-inflammatories and in the treatment of renal and respiratory disorders. Although it has been reported that species from the Erythroxylum genus induce cardiovascular effects, E. passerinum had not been studied specifically in this respect. However, previous phytochemical studies of E. passerinum demonstrated the presence of compounds which can have potential activity on the cardiovascular system. In this study, phytochemical screening of the ethanol extract of E. passerinum (EEEP) detected polyphenols, but not alkaloids. EEEP caused hypotension, bradycardia and vasorelaxation in rats. The vasorelaxation was attenuated by Nw-nitro-L-arginine methyl ester (L-NAME) or L-NAME + indomethacin (INDO), but not by INDO alone. Vasorelaxation was also significantly attenuated after endothelium removal or after incubation with high K+, 4-aminopyridine, glibenclamide or tetraethylammonium, but was not affected by pre-contraction with serotonin. Thus, EEEP induces hypotension and endothelium-dependent and independent vasorelaxation, which seems to involve the nitric oxide and K+-channels.

The Therapeutic Value of Hydralazine in Reducing Inflammatory Response, Oxidative Stress, and Mortality in Animal Sepsis: Involvement of the PI3K/AKT Pathway.

ABSTRACT: Sepsis is an amplified systemic immune-inflammatory response produced by a microorganism, which involves activation of inflammatory cytokine signaling pathways and oxidative stress. A variety of studies have shown that hydralazine (HDZ) has potent antioxidant and anti-inflammatory proprieties. Therefore, we hypothesize that HDZ can improve the clinical outcome of sepsis. Thus, this work aimed to evaluate therapeutic value of HDZ in reducing inflammatory response, oxidative stress, and mortality in animal sepsis, and to investigate its possible mechanism of action. Sepsis was induced by the cecal ligation and puncture (CLP) method in Wistar rats. After surgery, the animals were randomly divided into three groups: sham, sepsis, and sepsis + HDZ (1 mg/kg, s.c.). All groups were monitored for 48 h to assess survival rate, and clinical, hemodynamic, biochemical, and cellular parameters. After euthanasia, blood, spleen, liver, and kidneys were collected for analysis. Blood serum cytokines, tissue myeloperoxidase (MPO) activity, and oxidative stress parameters were assessed. Involvement of the PI3K/Akt pathway was also investigated. Sepsis was successfully induced by the CLP technique. HDZ treatment increased the survival rate (from 50% to 90%), improved glycemia control, reduced the clinical severity sepsis and mean arterial pressure; and prevented increased MPO activity, TNF-α, IL-1ß, IL-10 levels, and oxidative damage markers. Additionally, HDZ significantly prevented the increase of Akt activation in the liver and kidney. HDZ largely mitigated the effects of sepsis by suppressing inflammatory and antioxidant responses via the PI3K/Akt pathway. These findings provide evidence that HDZ can be a new therapeutic alternative for treating sepsis.

NOX-dependent reactive oxygen species production underlies arrhythmias susceptibility in dexamethasone-treated rats.

Dexamethasone is the most clinically used glucocorticoid with an established role in the treatment of a wide spectrum of inflammatory-related diseases. While the therapeutic actions are well known, dexamethasone treatment causes a number of cardiovascular side effects, which are complex, frequent and, in some cases, clinically unnoticeable. Here, we investigated whether a therapeutic regimen of dexamethasone affects cardiac arrhythmogenesis, focusing on the contribution of Nox-derived reactive oxygen species (ROS). Male Wistar rats were treated with dexamethasone (2 mg/kg, i.p.) for 7 days. Afterward, hemodynamic measurements, autonomic modulation, left ventricular function, cardiac fibrosis, reactive oxygen species (ROS) generation, Nox protein expression, superoxide dismutase (SOD) and catalase activities, and arrhythmias incidence were evaluated. Here, we show that dexamethasone increases blood pressure, associated with enhanced cardiac and vascular sympathetic modulation. Moreover, a marked increase in the cardiac ROS generation was observed, whereas the enhanced SOD activity did not prevent the higher levels of lipid peroxidation in the dexamethasone group. On the other hand, increased cardiac Nox 4 expression and hydrogen peroxide decomposition rate was observed in dexamethasone-treated rats, while Nox 2 remained unchanged. Interestingly, although preserved ventricular contractility and ß-adrenergic responsiveness, we found that dexamethasone-treated rats displayed greater interstitial and perivascular fibrosis than control. Surprisingly, despite the absence of arrhythmias at basal condition, we demonstrated, by in vivo and ex vivo approaches, that dexamethasone-treated rats are more susceptible to develop harmful forms of ventricular arrhythmias when challenged with pharmacological drugs or burst pacing-induced arrhythmias. Notably, concomitant treatment with apocynin, an inhibitor of NADPH oxidase, prevented these ectopic ventricular events. Together, our results reveal that hearts become arrhythmogenic during dexamethasone treatment, uncovering the pivotal role of ROS-generating NADPH oxidases for arrhythmias vulnerability.

d-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.

Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats / Efeitos Bradicárdicos e Antiarrítmicos do D-Limoneno em Ratos

Abstract Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resumo Fundamento: O D-limoneno (DL) é um monoterpeno e o principal componente do óleo essencial de frutas cítricas. Ele apresenta atividades anti-hiperglicêmicas e vasodilatadoras. Objetivos: Este estudo avaliou os efeitos cardiovasculares e antiarrítmicos potenciais do DL em ratos. Métodos: Os parâmetros hemodinâmicos e eletrocardiográficos (ECG) foram mensurados em ratos Wistar machos que, sob anestesia, tiveram a aorta abdominal e a veia cava inferior canuladas e receberam eletrodos implantados subcutaneamente. Na abordagem in vitro, o coração foi removido e perfundido utilizando a técnica de Langendorff. O nível de significância adotado foi de 5% (p < 0,05). Resultados: DL, nas doses de 10, 20 e 40 mg/kg (i.v), produziu bradicardia intensa e persistente associada à hipotensão. A bradicardia com QTc prolongado foi observada no registro in vivo do ECG. No modelo in vivo de arritmia induzida por Bay K8644, DL (10 mg / kg) houve diminuição do escore da arritmia de 15,33 ± 3,52 para 4,0 ± 2,64 u.a (p < 0,05, n = 4). Em corações perfundidos isolados, o DL (10-3 M) promoveu reduções significativas na frequência cardíaca (de 228,6 ± 8,5 ms para 196,0 ± 9,3 bpm; p < 0,05) e na pressão desenvolvida do ventrículo esquerdo (de 25,2 ± 3,4 para 5,9 ± 1,8 mmHg; n = 5, p < 0,05). Conclusões: O DL produz bradicardia e atividade antiarrítmica no coração de ratos.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats.

BACKGROUND: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. OBJECTIVES: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. METHODS: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). RESULTS: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). CONCLUSIONS: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resistance training improves cardiovascular autonomic control and biochemical profile of rats exposed to Western diet in the perinatal period. / Treinamento resistido melhora controle autonômico cardiovascular e perfil bioquímico de ratos expostos a dieta ocidental no período perinatal.

INTRODUCTION AND OBJECTIVES: Consumption of a Western diet during the perinatal period is associated with development of cardiovascular disease. Resistance training (RT) has been used to treat cardiovascular disorders. The aim of this work was to assess the effect of RT on cardiometabolic disorders in rats exposed to a Western diet in the perinatal period. METHODS: Female Wistar rats were fed with control or Western diet during pregnancy and lactation. The pups were divided into three groups: Control (C), Western Diet Sedentary (WDS) and Western Diet + RT (WDRT). At 60 days of age, all animals started the RT protocol (five times a week for four weeks). At the end, blood pressure was recorded for analysis of heart rate variability and baroreflex sensitivity (BRS). Blood samples were collected for biochemical analysis. RESULTS: RT reduced blood pressure and vascular sympathetic modulation and increased BRS. There were improvements in biochemical profile, with reductions in fasting blood glucose, total cholesterol and low-density lipoprotein, and an increase in high-density lipoprotein. CONCLUSION: RT led to beneficial adaptations in the cardiovascular system, mediated by changes in the mechanisms of autonomic control and biochemical profile of animals exposed to a Western diet in the perinatal period.

Resistance exercise mediates remote ischemic preconditioning by limiting cardiac eNOS uncoupling.

BACKGROUND: Currently viewed as a complementary non-pharmacological intervention for preventing cardiac disorders, long-term aerobic training produces cardioprotection through remote ischemic preconditioning (RIPC) mechanisms. However, RIPC triggered by acute exercise remains poorly understood. Although resistance exercise (RE) has been highly recommended by several public health guidelines, there is no evidence showing that RE mediates RIPC. Hence, we investigated whether RE induces cardiac RIPC through nitric oxide synthase (NOS)-dependent mechanism. METHODS AND RESULTS: Acute RE at 40% of the maximal load augmented systemic nitrite levels, associated with increased cardiac eNOS phosphorylation, without affecting nNOS activity. Using an experimental model of myocardial infarction (MI) through ischemia-reperfusion (IR), RE fully prevented the loss of cardiac contractility and the extent of MI size compared to non-exercised (NE) rats. Moreover, RE mitigated aberrant ST-segment and reduced life-threatening arrhythmias induced by IR. Importantly, inhibition of NOS abolished the RE-mediated cardioprotection. After IR, NE rats showed increased cardiac eNOS activity, associated with reduced dimer/monomer ratio. Supporting the pivotal role of eNOS coupling during MI, non-exercised rats displayed a marked generation of reactive oxygen species (ROS) and oxidative-induced carbonylation of proteins, whereas RE prevented these responses. We validated our data demonstrating a restoration of physiological ROS levels in NE + IR cardiac sections treated with BH4, a cofactor oxidatively depleted during eNOS uncoupling, while cardiac ROS generation from exercised rats remained unchanged, suggesting no physiological needs of supplemental eNOS cofactors. CONCLUSION: Together, our findings strongly indicate that RE mediates RIPC by limiting eNOS uncoupling and mitigates myocardial IR injury.

α-Terpineol reduces cancer pain via modulation of oxidative stress and inhibition of iNOS.

α-Terpineol (TP) is present in a wide range of essential oils of the genus Eucalyptus, with recognized potential for a range of biological effects, such as analgesic. Hence, our study aimed to investigate the effect of TP on cancer pain induced by sarcoma 180 in Swiss mice. Our results showed that TP reduced significantly mechanical hyperalgesia and spontaneous and palpation-induced nociception, improved paw use without reducing tumor growth and grip strength. Importantly, no evident biochemical and hematological toxicity was oberved. Furthermore, TP increased the tissue antioxidant capacity due to ferric-reducing antioxidant power (FRAP) and glutathione (GSH). TP also reduced inducible nitric oxide synthase (iNOS) immunocontent in the tumors. Molecular docking estimated that TP binds within the same range of iNOS regions (other iNOS inhibitors), such as N-Nitroarginine methyl ester (L-NAME). These data provide strong evidence that TP may be an interesting candidate for the development of new safe analgesic drugs that are effective for cancer pain control.

Levobupivacaine induces vasodilatation, but not vasoconstriction, in rat mesenteric artery / Levobupivacaína induz vasodilatação, mas não vasoconstrição em artéria mesentérica de rato

Introduction: Levobupivacaine (LEVO) can replace analgesia because it exhibits low toxicity and causes minor vasoconstriction, enabling its use in patients in whom vasoconstrictors are contraindicated. Objective: We aimed to evaluate the effects of LEVO in isolated rat superior mesenteric artery by using the vascular reactivity technique and compare its effect to that of lidocaine. Material and method: Arterial rings were obtained from the mesenteric artery of male Wistar rats and kept in organ baths. For recording isometric contractions, each ring was suspended by cotton threads from a force transducer, which was connected to a data acquisition system. Result: Both lidocaine and LEVO did not show a vasoconstrictor effect on the basal tone of the arterial rings with functional endothelium. However, when the rings were pre-contracted with phenylephrine, both drugs were able to induce concentration-dependent vasodilatation. The vasodilator effect induced by LEVO did not change after removal of the endothelium, or with the addition of tetraethylammonium (1 mM), a non-selective K+ channel blocker. In the rings without functional endothelium, which were pre-contracted with depolarizing Tyrode's solution (KCl 80 mM), LEVO-induced vasodilatation was not significantly different from that observed in the rings pre-contracted with phenylephrine. Moreover, it did not show a significant additional vasodilator effect compared to the maximal vasodilator effect of nifedipine. Conclusion: This study demonstrated that LEVO produces a vasodilator effect in the rat superior mesenteric artery in an endothelium-independent manner. This effect seems to be mediated via Ca2+ channel blockade in the vascular smooth muscle cells.

Introdução: Levobupivacaína pode ser uma nova alternativa para analgesia por apresentar baixa toxicidade e vasoconstrição, permitindo sua utilização em pacientes que apresentam contra-indicação no uso de vasoconstritores. Objetivo: Avaliar os efeitos da levobupivacaína utilizando a técnica de reatividade vascular em artéria mesentérica isolada de rato e comparar este efeito à lidocaína. Material e método: Anéis foram obtidos da artéria mesentérica de ratos machos Wistar e foram mantidos em cubas. Para o registro das contrações isométricas, cada anel foi suspenso por linhas de algodão fixadas a um transdutor de força acoplado a um sistema de aquisição. Resultado: Tanto a lidocaína como a levobupivacaína não apresentaram efeito vasocontritor sobre o tônus basal em anéis com endotélio functional. No entanto, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas induziram um vasorrelaxamento concentração-dependente. O efeito vasorrelaxante causado pela levobupivacaína não foi diferente após a remoção do endotélio, ou com o tetraetilamônio (1mM), um bloqueador não seletivo dos canais para. K+. Em anéis sem endotélio funcional e pré-contraídos com solução despolarizante de Tyrode (KCl 80mM), o vasorelaxamento induzido pela levobupivacaína não foi significativamente diferente daquele observado em anéis pré-contraídos com fenilefrina e não apresentou um efeito adicional significativo sobre o relaxamento máximo da nifedipina. Conclusão: Este estudo demonstrou que a levobupivacaína produz efeito vasorrelaxante em artéria mesentérica de rato, que é endotélio independente. Este efeito parece envolver os bloqueadores de canais para Ca2+ em célula muscular vascular lisa.

Avaliação dos efeitos da ropivacaína sobre a reatividade vascular em artéria mesentérica de rato / Assessment of the effects of ropivacaine on vascular reactivity in rat mesenteric artery

Introdução: A ropivacaína (ROPI) é um anestésico local de longa duração de ação, introduzido mais recentemente em Medicina, mas ainda não disponível para uso odontológico em tubetes. Estudos clínicos e com animais confirmam que a ROPI é um anestésico local eficaz e que possui um efeito vasoconstritor intrínseco. Objetivo: Avaliar os efeitos da ROPI sobre a reatividade vascular em artéria mesentérica isolada de rato, além de comparar esse efeito ao da lidocaína (LIDO) e avaliar o possível envolvimento do endotélio vascular na resposta induzida pela ROPI em anel de artéria mesentérica isolada de rato. Material e Método: Foram utilizados 14 ratos Wistar machos (250-300g). Os animais foram eutanasiados e, através de uma incisão no abdome do animal, foi retirada a artéria mesentérica. Desta artéria, foram obtidos anéis (1-2 mm), que foram mantidos em cubas contendo 10 mL de solução nutritiva de Tyrode mantida a 37 °C e gaseificada com carbogênio. Para o registro das contrações isométricas, cada anel foi suspenso, por linhas de algodão, a um transdutor de força conectado a um sistema de aquisição. RESULTADO: Tanto a LIDO como a ROPI não apresentaram efeito vasoconstritor sobre o tônus basal de anéis com endotélio funcional. Porém, quando os anéis foram pré-contraídos com fenilefrina, ambas as drogas foram capazes de induzir vasorrelaxamentos dependentes da concentração (Emáx = 31,7 ± 3,3%; n = 6, para a LIDO; Emáx = 69 ± 8%; n = 6, para a ROPI), que não foram alterados após a remoção do endotélio (Emáx = 28,7 ± 1,3%; n = 7, para a LIDO; Emáx = 58,8 ± 5,9%; n = 6, para a ROPI). Em anéis sem endotélio ...

Introduction: Ropivacaine (ROPI) is a local anesthetic of long duration of action, more recently introduced in medicine, however is not available for dental use in tubes yet. Clinical and animal studies have confirmed that bupivacaine is an effective anesthetic that also has an intrinsic vasoconstrictor effect. Objective: To evaluate the effects of ropivacaine on vascular reactivity in isolated rat mesenteric artery, compare this to the effect of lidocaine (LIDO) and evaluate the possible involvement of the vascular endothelium induced by ROPI in isolated rat mesenteric artery ring response. Material and Method: It was used 12 male Wistar rats (250-300g). The animals were euthanized and through an incision in the abdomen of the animal, the mesenteric artery was removed. Artery rings (1-2 mm) were obtained by the mesenteric artery, which were kept in vats containing 10 ml of Tyrode's nutrient solution kept at 37 °C and gassed with carbogen. For the recording of isometric contractions, each ring was suspended by cotton lines to a force transducer connected to a data acquisition system. RESULT: Both the LIDO as ROPI showed no vasoconstrictor effect on the basal tone of rings with functional endothelium. However, when the rings were precontracted with phenylephrine, both drugs were able to induce concentration-dependent vasorelaxation (Emax = 31.7 ± 3.3%, n = 6 for LIDO and 69 ± 8%, n = 6 for ROPI) that were not altered after removal of the endothelium (Emax = 28.7 ± 1.3%, n = 7 for LIDO and Emax = 58.8 ± 5.9%, n = 6 for ROPI). In rings without functional endothelium and precontracted with depolarizing Tyrode solution (80 mM KCl), the LIDO-induced vasorelaxation was no significantly changed (Emax = 29 ± 3%, n = 7). However, ROPI-induced vasorelaxation was reduced in this protocol and the presence of 1 mM tetraethylammonium (TEA) (Emax = 21.2 ± 5.1%, n = 7 and Emax = 17.4 ± 3.7, n = 4, ...

Treinamento aeróbio previne alterações na vasodilatação dependente do endotélio em ratos diabéticos / Aerobic training prevents changes in endothelium-dependent vasodilation of diabetic rats

O objetivo do presente estudo é verificar os efeitos do treinamento aeróbio sobre a reatividade vascular em artéria mesentérica de ratos diabéticos. Ratos Wistar foram divididos em três grupos: controle sedentário (CS), diabético sedentário (DS) e diabético treinado (DT). Alterações na reatividade vascular foram avaliadas após a última sessão de treinamento, por meio da obtenção de curvas concentração-resposta. Os testes t de Student ou análise de variância (ANOVA) de duas-vias, seguida do pós-teste de Bonferroni, foram realizados para avaliar a significância das diferenças entre as médias. Foi observada uma redução dos relaxamentos induzidos por acetilcolina no grupo DS (79,7 ± 3,0 %), quando comparado ao CS (98,8 ± 3,0) e uma manutenção dos valores normais no grupo DT (100,1 ± 5,3 %). Os resultados sugerem que o treinamento aeróbio é capaz de proporcionar efeitos benéficos na função vascular de ratos diabéticos.

The aim of this study was to investigate the effects of aerobic training on the vascular reactivity in the mesenteric artery from diabetic rats. Wistar rats were divided into three groups: sedentary control (SC), sedentary diabetic (SD) and trained diabetic (TD). Changes in vascular reactivity were assessed after the last training session by obtaining concentration-response curves. Student's t-test or two-way analysis of variance (ANOVA) followed by the Bonferroni post-test were performed to evaluate the significance of differences between means. A reduction was observed in the relaxation induced by acetylcholine in the SD group (79.7 ± 3.0%) compared to SC (98.8 ± 3.0%), and maintenance of normal values ​​in the TD group (100.1 ± 5.3%). The results suggest that exercise training can have beneficial effects on vascular function in diabetic rats.

Experimental gestational hypothyroidism evokes hypertension in adult offspring rats.

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n=13) or water-treated dams (OWTD, n=13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 ± 2.0 vs 108.8 ± 3.0 mmHg, p<0.001), SAP (157.3 ± 2.9 vs 135.7 ± 4.5mm Hg, p<0.001) and DAP (109.7 ± 1.9 vs 88.4 ± 2.6 mmHg, p<0.001) when compared to OWTD, and had lower HR (355.1 ± 8.9 vs 386.8 ± 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 ± 0.8 vs 4.0 ± 0.6 mmHg(2), p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems.

Efeitos cardiovasculares induzidos pelo óleo essencial de Ocotea Duckei Vattimo em ratos / Cardiovascular effects induced by essential oil of Ocotea Duckei Vattimo in Rats

Objetivo: Avaliar os efeitos cardiovasculares induzidos pelo óleo essencial das folhas de Ocotea dukei Vattimo (OEOD) em ratos. Material e Métodos: O óleo essencial foi obtido de folhas frescas usando aparelho de clevenger. Ratos machos Wistar (250-350 g) foram cateterizados para registro direto de pressão arterial ou sacrificados para retirada e montagem de átrio isolado de rato. Resultados: Em ratos não-anestesiados, OEOD (1, 5, 10 e 15 mg/kg i.v., randomicamente, n = 6) induziu hipotensão e bradicardia. A hipotensão não foi afetada por atropina (2 mg/Kg, i.v.) nem por L-NAME (20 mg/Kg, i.v.), enquanto que a bradicardia foi abolida somente pela antropina. Em ratos anestesiados e vagotomizados, somente a bradicardia foi atenuada. Em átrio isolado de rato, OEOD (1 - 500 µg/mL) induziu efeitos cronotrópico e inotrópico negativos que não foram afetados pela atropina (1 µM). Além disso, nestas preparações, OEOD (1, 10, 30 e 100 µg/mL) inibiu as curvas concentração-resposta para CaCi2. Conclusão: Estes resultados demonstram que o OEOD induz hipotensão, que parece ser devido a uma diminuição da resistência periférica vascular, e bradicardia, que parece ser devido a uma ativação indireta dos recptores muscarínicos cardíacos via estimulação vagal. Além disso, o OEOD induz efeitos cronotrópico e inotrópico negativos em átrio de rato provavelmente devido a uma inibição do influxo de cálcio, a qual parece contribuir também para a bradicardia induzida pelo OEOD