Glucocorticoids have important anti-inflammatory and immunomodulatory activities. Dexamethasone (Dex), a synthetic glucocorticoid, induces insulin resistance, hyperglycemia, and hypertension. The ...hypertensive mechanisms of Dex are not well understood. Previously, we showed that exercise training prior to Dex treatment significantly decreases blood vessel loss and hypertension in rats. In this study, we examined whether the salutary effects of exercise are associated with an enhanced metabolic profile. Analysis of the NAD and ATP content in the tibialis anterior muscle of trained and non-trained animals indicated that exercise increases both NAD and ATP; however, Dex treatment had no effect on any of the experimental groups. Likewise, Dex did not change NAD and ATP in cultured endothelial cells following 24 h and 48 h of incubation with high concentrations. Reduced VEGF-stimulated NO production, however, was verified in endothelial cultured cells. Reduced NO was not associated with changes in survival or the BH4 to BH2 ratio. Moreover, Dex had no effect on bradykinin- or shear-stress-stimulated NO production, indicating that VEGF-stimulated eNOS phosphorylation is a target of Dex's effects. The PTP1B inhibitor increased NO in Dex-treated cells in a dose-dependent fashion, an effect that was replicated by the glucocorticoid receptor inhibitor, RU486. In combination, these results indicate that Dex-induced endothelial dysfunction is mediated by glucocorticoid receptor and PTP1B activation. Moreover, since exercise reduces the expression of PTP1B and normalized insulin resistance in aging rats, our findings indicate that exercise training by reducing PTP1B activity counteracts Dex-induced hypertension in vivo.
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•Dexamethasone (Dex) induces hypertension that is ameliorated by exercise training.•Dex causes skeletal muscle (tibialis anterior) microvascular rarefaction.•Dex does not modify NAD or ATP levels in vivo or in cultured endothelial cells.•Dex alters VEGF but not bradykinin or shear stress-mediated NO activation.•Glucocorticoid receptor or PTPB1 inhibition improves NO signaling in Dex-treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The goal of this article is to analyse the musical preferences of Brazilian students by considering the variables of gender and religion. Using random sampling, a class was selected from each high ...school year group of 10 public schools in the city of São Luís (Brazil).The total study sample consisted of 658 students: 358 females (54.4%) and 300 males (45.6%). Of these, 343 (52.1%) were Protestants and 315 (47.9%) were Catholics, and their ages ranged from 14 to 19 years (M = 16.24 years old, SD = 1.14). For the data collection, a version of the Questionnaire on Musical Style Preferences by Lorenzo, Herrera, and Cremades (2008) was used; however, it was shortened and culturally adapted to the Brazilian context. The participants were asked to evaluate how often they listened to 19 different styles of music. The overall results indicated that the participants’ musical preferences were heavily influenced by mass media. However, ANOVA results indicated significant differences and a variety of size effects in the frequency of musical listening based on gender and religion. Females had a greater preference for styles with emotional content, dance music and music with a strong connection to mass culture, while males preferred more vigorous styles. Regarding religion, Protestants had a stronger preference for gospel music, while Catholic preferences were more diverse.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Dexamethasone (DEX) treatment often increases blood pressure. Exercise training is an efficient non‐pharmacological intervention to treat hypertension, which is thought to be explained by improved ...microvascular function. Microcirculation related‐microRNAs (miRNAs) play a role in maintaining micro vessel skeletal density. The aim of this study was to investigate if training‐induced miRNAs are associated with exercise training‐dependent prevention of DEX‐induced rarefaction. Wistar rats were trained (treadmill) for 8 weeks or not (sedentary) and then treated with DEX (50 μg/kg per day, s.c.) or saline for 14 days. Carotid artery catheterization for arterial pressure measurements was performed on last day of treatment and tibialis anterior (TA) muscle was collected for morphometric, protein and microRNAs analyses. In sedentary rats, DEX treatment induced hypertension (+27%) concomitantly with capillary density loss (CD, −20.8%) and decreased VEGF (−43.0%), p‐AKT/AKT (−39.6%) and Bcl‐2 (−23.0%) protein levels and increased caspase‐3‐cleaved protein (+34.0%) in TA muscle. In the trained group, however, microRNA‐126 expression was increased (+13.1%), which was followed by enhanced p‐AKT/AKT (+37.7%) and Bcl‐2 (+7.7%), as well as a diminished caspase‐3‐cleaved (−23.1%) protein level. The changes in miRNA‐126 expression were positively correlated with p‐AKT/AKT (r=0.7246) and VEGF (r=0.5224) protein levels. Neither DEX nor training significantly changed miRNA‐16, 21, 221, 222, 155. We concluded that miRNA‐126 upregulation, induced by training, plays an important role in controlling skeletal muscle vessel density. MiRNA126 could be a novel therapeutic agent against DEX‐induced rarefaction.
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Financial support: FAPESP (2018/06998‐7)
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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Dexamethasone (DEX) is widely used due to its potent anti-inflammatory effect,;
although its chronic use may cause unwanted effects, including arterial hypertension (H);
and muscle atrophy. The mechanisms responsible for these effects remain unclear.;
Nervous system, microcirculation and oxidative stress may be involved in H. In;
addition, oxidative stress may also be responsible for muscle atrophy. On the other;
hand, exercise training (T) its recommended for H treatment and it is an oxidative stress;
modulator. The aim of this study was to investigate if DEX-induced H is associated;
with changes in the autonomic nervous system, microcirculation and oxidative stress.;
Moreover, it evaluated if arterial pressure (AP) reduction induced by T is associated;
with a better balance of these mechanisms. Still, it investigated if muscle atrophy was;
also involved with oxidative stress and if T could improve this response. Rats were;
submitted to T for 8 weeks or kept sedentary and then treated or not with DEX;
(50μg/kg/day for 14 days), composing four groups: sedentary control (SC), sedentary;
DEX (SD), trained control (TC) and trained DEX (TD). Body weight (BW), basal AP,;
autonomic balance to the heart and sympathetic nerve activity to the vessels were;
analyzed. Aorta was collected for evaluation of oxidative stress and tibialis anterior;
(TA) and soleus (SOL) muscles were collected for microcirculation histological;
analysis and for gene and protein evaluations of gp91phox, p47phox, SOD-1, SOD-2;
and CAT. DEX decreased BW (-29.1g), increased AP (+12.1%), TA muscle atrophy (-;
8.2%), increased low-frequency waves to the heart (+58.5%) and vessels (+96.6%),;
decreased high-frequency waves to the heart (-12.0%), reduced capillary density and;
capillary-fiber-ratio (C:F ratio) in TA (respectively -21.9%, -11.1%) and SOL;
(respectively -25.9%, -22.2%) muscles. In contrast, T mitigated AP increase (-10.0%),;
atennuated low-frequency waves increase to the heart (-21.5%) and vessels (-8.4%) and;
also high-frequency waves decrease to the heart (+8.4%). Moreover, T prevented;
capillary density and C:F ratio reductions in TA (respectively, +46.0% +31.6%) and;
SOL (respectively, +44.4% +37.5%) muscles and increased SOD-2 and CAT protein;
level in TA (respectively + 37.4%, + 20.9%) and SOL (respectively +15.4%, +18.0%);
muscles. The results allow us to suggest that DEX-induced H may be associated with;
changes in sympathetic nervous system to the heart and vessels, parasympathetic;
nervous system to the heart and also microcirculation rarefaction. In the other hand, T;
was able to mitigate AP increase due to autonomic balance improvement and rarefaction;
prevention. Since T increased rat´s antioxidant capacity independent of attenuation of;
muscle atrophy, we may suggest that oxidative stress is not involved in DEX-induced;
muscle atrophy.
A dexametasona (DEX) é amplamente utilizada devido ao seu potente efeito antiinflamatório,;
contudo seu uso crônico pode acarretar efeitos deletérios, dentre eles a;
hipertensão arterial (HA) e a atrofia muscular. Os mecanismos responsáveis por esses;
efeitos permanecem incompreendidos. O sistema nervoso, a microcirculação e o;
estresse oxidativo parecem estar envolvidos com a HA. O estresse oxidativo também;
pode ser responsável pela atrofia muscular. Por outro lado, o treinamento físico (TF) é;
recomendado no tratamento da HA e é considerado moderador do estresse oxidativo. O;
objetivo do estudo foi investigar se a HA induzida pela DEX está associada com;
alterações no sistema nervoso autônomo, na microcirculação e ao estresse oxidativo.;
Além disso, avaliar se a diminuição da PA induzida pelo TF está associada a um melhor;
ajuste nestes mecanismos. Ainda, investigar se a atrofia muscular também estaria;
envolvida com o estresse oxidativo e se o TF poderia contribuir para melhora dessa;
alteração. Ratos Wistar foram submetidos a um protocolo de TF ou mantidos sedentário;
por 8 semanas. Os animais foram tratados ou não com DEX (50μg/kg, por dia, por 14;
dias) compondo 4 grupos: sedentário controle (SC), sedentário DEX (SD), treinado;
controle (TC) e treinado DEX (TD). Foram analisados peso corporal (PC), pressão;
arterial em repouso, balanço autonômico para o coração e atividade simpática para os;
vasos. A aorta foi coletada para avaliação do estresse oxidativo e os músculos tibial;
anterior (TA) e sóleo (SOL) coletados para realização das análises histológicas na;
microcirculação e avaliações gênicas e proteicas da gp91phox, p47phox, SOD-1, SOD-;
2 e CAT. A DEX provocou redução do PC (-29,1g), aumento da PA (+12,1%), atrofia;
muscular no TA (-8,2%), aumento das ondas de baixa frequência para o coração;
(+58,5%) e para os vasos (+96,6%), diminuição das ondas de alta frequência para o;
coração (-12,0%), redução da densidade capilar e da razão capilar fibra nos músculos;
TA (respectivamente, -21,9%, -11,1%) e SOL (respectivamente -25,9%, -22,2%). O TF;
atenuou o aumento da PA (-10,0%), o aumento das ondas de baixa frequência para o;
coração (-21,5%) e para os vasos (-8,4%) e a diminução das ondas de alta frequência;
para o coração (+8,4%), além de prevenir a redução da densidade capilar e da razão;
capilar fibra, tanto no TA (respectivamente, +46,0%, +31,6%) como no SOL;
(respectivamente, +44,4%, +37,5%) e aumentar a produção protéica da SOD-2 e CAT;
no TA (respectivamente, +37,4%, +20,9%) e no SOL (respectivamente, +15,4%,;
+18,0%). Assim, podemos concluir que a HA induzida por DEX pode estar relacionada;
tanto com alterações no sistema nervoso autônomo para o coração e no sistema;
simpático para os vasos, como com a rarefação encontrada na microcirculação e que o;
TF foi capaz de atenuar esse aumento da PA devido a uma melhora no balanço;
autonômico para o coração e a prevenção da rarefação na microcirculação. O aumento;
da capacidade antioxidante induzido pelo TF independente da atenuação da atrofia;
muscular sugere que o estresse oxidativo parece não influenciar a atrofia muscular;
induzida pela DEX.
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