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Physical precinditioning effects on Dexamethasone-induced hypertensio: role of Renin-Angiotensin System

Grant number: 12/19722-3
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): May 01, 2013
Effective date (End): February 28, 2014
Field of knowledge:Health Sciences - Physical Education
Principal Investigator:Sandra Lia do Amaral Cardoso
Grantee:Paula Bessi Constantino Prazeres
Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil


The synthetic glucocorticoids are widely used in treating inflammation and allergy, but its chronic use determines various side effects on the metabolism of sugar, fat and protein. We demonstrated recently that treatment for 10 days with dexamethasone (Dexa) causes hyperglycemia accompanied by hyperinsulinemia, muscle atrophy and hypertension, however, the mechanisms responsible for these responses are not yet fully understood. It has been described that renin-angiotensin system (RAS) is an important blood pressure regulator and that an increase in its activity might be a possible mechanism for the increased blood pressure (BP) induced by Dexa. On the other hand, the aerobic exercise, of low to moderate intensity, has been recommended as an adjunct in the treatment of hypertension and its effects on the RAS has been demonstrated in the literature. We have shown recently that physical preconditioning contributes to reduce Dexa-induced hypertension, however little is known about the mechanisms responsible for this response. Therefore, the aim of this work is to investigate if the mechanisms triggered by aerobic exercise to attenuate Dexa-induced hypertension involve RAS. Male Wistar rats (200g) will be submitted to a protocol of aerobic exercise on the treadmill (60% of maximum capacity for 70 days, 5 days a week, 1 hour per day) or kept as sedentary. Moreover, during the last 10 days, the animals will be treated with DEXA (1.0 mg / kg of body weight per day, ip) or saline, thus composing 4 groups, namely: sedentary control (SC), sedentary treated (SD), trained control (TC) and trained and treated (TD). An additional group of animals will be pharmacologically treated with losartan during treatment with Dexa. We will analyze body weight, fasting glucose and resting blood pressure before and after treatment for 10 days with Dexa. After hemodynamic procedure, the animals will be anesthetized for collection and processing of skeletal muscles (tibialis anterior, soleus and Flexor hallus longus) for evaluation of gene and protein expression of different components of the RAS. Results will be presented as mean ± EPM. ANOVA two way will be performed for comparison between groups and post-hoc Tukey will be used when necessary.

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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)
DUCHATSCH, FRANCINE; CONSTANTINO, PAULA B.; HERRERA, NAIARA A.; FABRICIO, MAYARA F.; TARDELLI, LIDIELI P.; MARTUSCELLI, ALINE M.; DIONISIO, THIAGO J.; SANTOS, CARLOS F.; AMARAL, SANDRA L.. Short-term exposure to dexamethasone promotes autonomic imbalance to the heart before hypertension. JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION, v. 12, n. 8, p. 605-613, . (14/23050-6, 15/03965-2, 12/19722-3, 14/23229-6)
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)

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