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Effects of physical exercise on hypertension and oxidative stress in dexamethasone-treated rats

Grant number: 14/18177-7
Support Opportunities:Scholarships in Brazil - Master
Start date: November 01, 2014
End date: February 29, 2016
Field of knowledge:Health Sciences - Physical Education
Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Sandra Lia do Amaral Cardoso
Grantee:Naiara Araújo Herrera
Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

Dexamethasone (DEX) is widely used in clinical due to its potent anti-allergic and anti-inflammatory effects, but its chronic use may cause various harmful side-effects. Ten days of DEX Treatment contributes to the development of Hypertension (HA), however the mechanism responsible for this effect are not yet fully understood. Studies suggest that a possible mechanism responsible for this hypertension may be an imbalance between production and removal of Reactive Oxygen Species (ROS). On the other hand, aerobic exercise training has been recommended as a coadjuvant in the treatment of hypertension and it has also been shown that it is beneficin reducing oxidative stress. Therefore, the aim of this study is to investigate if DEX-induced hypertension is associated with an imbalance between the production of ROS, mostly by NADPH oxidase enzyme complex and the removal by the antioxidant enzymes. Moreover, to evaluate if the decrease in Blood Pressure (BP) induced by physical training is associated with a better balance between these parameters. Male Wistar rats (200g) will be submitted to an aerobic exercise protocol on a treatmill (60% of maximum capacity, 74 days, 5 days per week, 1 hour per day) or kept as sedentary. During the last 14 days, the animals will be treated with DEX (50¼g/kg per day, s.c.) or saline. Body weight will be measured weekly during the physical training and daily during the treatment. The resting BP will be measured through catheterization in the carotid artery after treatment with DEX. Subsequently, after euthanasia, soleus and tibialis anterior muscles will be removed and processed for evaluation of gene expression and protein production of subunits gp91phox and p47phox of the enzyme complex NADPH oxidase and antioxidant enzymes SOD-1, SOD-2 and CAT. In addition, samples of muscles will be histologically processed to evaluate the total formation of ROS by the oxidation of dihidroetidina and wall-lumen ratio of arterioles, which will be correlated with BP values. Results will be presented as mean ±EPM. ANOVA two way will be performed for comparison among groups and post-hoc Tukey (±<0,05) will be used when necessary. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CONSTANTINO, PAULA B.; DIONISIO, THIAGO J.; DUCHATSCH, FRANCINE; HERRERA, NAIARA A.; DUARTE, JOSIANE O.; SANTOS, CARLOS F.; CRESTANI, CARLOS C.; AMARAL, SANDRA L.. Exercise attenuates dexamethasone-induced hypertension through an improvement of baroreflex activity independently of the renin-angiotensin system. Steroids, v. 128, p. 147-154, . (14/23050-6, 12/19722-3, 12/14376-0, 11/21522-0, 14/18177-7)
JESUS, ISLEY; HERRERA, NAIARA A.; ANDREO, JESUS C.; SANTOS, CARLOS F.; AMARAL, SANDRA L.. Training counteracts DEX-induced microvascular rarefaction by improving the balance between apoptotic and angiogenic proteins. Steroids, v. 156, . (14/18177-7, 14/23229-6)
HERRERA, NAIARA A.; JESUS, ISLEY; SHINOHARA, ANDRE L.; DIONISIO, THIAGO J.; SANTOS, CARLOS F.; AMARAL, SANDRA L.. Exercise training attenuates dexamethasone-induced hypertension by improving autonomic balance to the heart, sympathetic vascular modulation and skeletal muscle microcirculation. Journal of Hypertension, v. 34, n. 10, p. 1967-1976, . (14/23229-6, 14/18177-7)